Variant 3-46860639-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.260

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.307+37A>C		intron_variant		ENST00000292327.6

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51348

AN:

151966

Hom.:

14710

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.174

AC XY:

126456

AN XY:

724998

show subpopulations

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.:

AF XY:

0.340

AC XY:

25311

AN XY:

74356

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over