rs936175

chr3-46863218-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000258.3(MYL3):c.129+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,612,216 control chromosomes in the GnomAD database, including 39,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (11679 hom., cov: 32)
  • Exomes 𝑓: 0.16 (27565 hom.)
• Consequence: MYL3 NM_000258.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0150

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-46863218-C-A is Benign according to our data. Variant chr3-46863218-C-A is described in ClinVar as [Benign]. Clinvar id is 255637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863218-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL3	NM_000258.3	c.129+44G>T		intron_variant		ENST00000292327.6
MYL3	NM_001406937.1	c.129+44G>T		intron_variant
MYL3	NM_001406938.1	c.129+44G>T		intron_variant
MYL3	NM_001406939.1	c.129+44G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL3	ENST00000292327.6	c.129+44G>T		intron_variant		1	NM_000258.3	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45577 AN: 152054 Hom.: 11646 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.275

GnomAD3 exomes AF: 0.207 AC: 51676 AN: 249054 Hom.: 8620 AF XY: 0.209 AC XY: 28169 AN XY: 134848

Gnomad AFR exome AF: 0.696

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.395

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.157 AC: 228752 AN: 1460044 Hom.: 27565 Cov.: 32 AF XY: 0.163 AC XY: 118089 AN XY: 726378

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.300 AC: 45660 AN: 152172 Hom.: 11679 Cov.: 32 AF XY: 0.301 AC XY: 22423 AN XY: 74402

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.274

Alfa AF: 0.197 Hom.: 2293

Bravo AF: 0.317

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Hypertrophic cardiomyopathy 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs936175; hg19: chr3-46904708; COSMIC: COSV52767741;