3-46860639-T-G

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.307+37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,609,092 control chromosomes in the GnomAD database, including 48,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (14755 hom., cov: 32)
  • Exomes 𝑓: 0.17 (33888 hom.)
• Consequence: MYL3 NM_000258.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.260

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=-0.88).
• BP6: Variant 3-46860639-T-G is Benign according to our data. Variant chr3-46860639-T-G is described in ClinVar as [Benign]. Clinvar id is 255638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46860639-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL3	NM_000258.3	c.307+37A>C		intron_variant		ENST00000292327.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL3	ENST00000292327.6	c.307+37A>C		intron_variant		1	NM_000258.3	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51348 AN: 151966 Hom.: 14710 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.300

GnomAD3 exomes AF: 0.253 AC: 62292 AN: 246266 Hom.: 12022 AF XY: 0.245 AC XY: 32792 AN XY: 133720

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.379

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.170 AC: 247368 AN: 1457008 Hom.: 33888 Cov.: 34 AF XY: 0.174 AC XY: 126456 AN XY: 724998

Gnomad4 AFR exome AF: 0.799

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.338 AC: 51450 AN: 152084 Hom.: 14755 Cov.: 32 AF XY: 0.340 AC XY: 25311 AN XY: 74356

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.299

Alfa AF: 0.162 Hom.: 5785

Bravo AF: 0.368

Asia WGS AF: 0.371 AC: 1288 AN: 3478

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	-0.88
Cadd	Benign	3.6
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2227294; hg19: chr3-46902129; COSMIC: COSV52767695; COSMIC: COSV52767695;