chr3-46860997-G-A

Variant names:

• chr3-46860997-G-A
• rs374988162
• NM_000258.3:c.130-10C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000258.3(MYL3):​c.130-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYL3 NM_000258.3 intron
• Scores: Splicing: ADA: 0.000005699
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

MYL3 (HGNC:7584): (myosin light chain 3) MYL3 encodes myosin light chain 3, an alkali light chain also referred to in the literature as both the ventricular isoform and the slow skeletal muscle isoform. Mutations in MYL3 have been identified as a cause of mid-left ventricular chamber type hypertrophic cardiomyopathy. [provided by RefSeq, Jul 2008]

MYL3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 8

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-46860997-G-A is Benign according to our data. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860997-G-A is described in CliVar as Likely_benign. Clinvar id is 415513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL3	NM_000258.3	c.130-10C>T		intron_variant	Intron 1 of 6	ENST00000292327.6	NP_000249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL3	ENST00000292327.6	c.130-10C>T		intron_variant	Intron 1 of 6	1	NM_000258.3	ENSP00000292327.4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250998 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461770 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74400

African (AFR) AF: 0.0000964 AC: 4 AN: 41500

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000267 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 18, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hypertrophic cardiomyopathy Benign:1

Jan 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000057
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374988162; hg19: chr3-46902487;