18-3215158-C-G

Position:

chr18-3215158-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003803.4(MYOM1):c.66G>C(p.Val22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,430 control chromosomes in the GnomAD database, including 7,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 847 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7099 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

MYOM1 (HGNC:7613): (myomesin 1) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MYOM1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 18-3215158-C-G is Benign according to our data. Variant chr18-3215158-C-G is described in ClinVar as [Benign]. Clinvar id is 226835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM1	NM_003803.4 linkuse as main transcript	c.66G>C	p.Val22=	synonymous_variant	2/38	ENST00000356443.9	NP_003794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9 linkuse as main transcript	c.66G>C	p.Val22=	synonymous_variant	2/38	1	NM_003803.4	ENSP00000348821	P2	P52179-1
MYOM1	ENST00000261606.11 linkuse as main transcript	c.66G>C	p.Val22=	synonymous_variant	2/37	1		ENSP00000261606	A2	P52179-2
	ENST00000580139.1 linkuse as main transcript	n.198-1834C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15733

AN:

152070

Hom.:

849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.0816

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0898

Gnomad OTH

AF:

0.0842

GnomAD3 exomes

AF:

0.0991

AC:

24525

AN:

247512

Hom.:

1310

AF XY:

0.0989

AC XY:

13297

AN XY:

134466

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0724

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0973

Gnomad NFE exome

AF:

0.0917

Gnomad OTH exome

AF:

0.0966

GnomAD4 exome

AF:

0.0961

AC:

140397

AN:

1461242

Hom.:

7099

Cov.:

AF XY:

0.0963

AC XY:

70015

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.0727

Gnomad4 ASJ exome

AF:

0.0931

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.0919

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.103

AC:

15736

AN:

152188

Hom.:

847

Cov.:

AF XY:

0.104

AC XY:

7729

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0929

Gnomad4 ASJ

AF:

0.0816

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0924

Gnomad4 NFE

AF:

0.0897

Gnomad4 OTH

AF:

0.0819

Alfa

AF:

0.0757

Hom.:

166

Bravo

AF:

0.103

Asia WGS

AF:

0.154

AC:

536

AN:

3478

EpiCase

AF:

0.0860

EpiControl

AF:

0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Val22Val in exon 2 of MYOM1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 12.0% (504/4212) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs1662316). -

MYOM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 21, 2013

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

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

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