NM_003803.4:c.1392G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003803.4(MYOM1):c.1392G>A(p.Arg464Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,609,800 control chromosomes in the GnomAD database, including 35,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3510 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31905 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.573

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 18-3164387-C-T is Benign according to our data. Variant chr18-3164387-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 226800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.573 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.1392G>A	p.Arg464Arg	synonymous_variant	Exon 10 of 38	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9 link	c.1392G>A	p.Arg464Arg	synonymous_variant	Exon 10 of 38	1	NM_003803.4	ENSP00000348821.4		P52179-1
MYOM1	ENST00000261606.11 link	c.1392G>A	p.Arg464Arg	synonymous_variant	Exon 10 of 37	1		ENSP00000261606.7		P52179-2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31880

AN:

152084

Hom.:

3497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.180

AC:

43521

AN:

242424

Hom.:

4316

AF XY:

0.181

AC XY:

23739

AN XY:

131434

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.00534

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.204

AC:

296877

AN:

1457598

Hom.:

31905

Cov.:

AF XY:

0.203

AC XY:

147231

AN XY:

724694

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.00449

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.210

AC:

31929

AN:

152202

Hom.:

3510

Cov.:

AF XY:

0.205

AC XY:

15221

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.00520

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.213

Hom.:

1833

Bravo

AF:

0.216

Asia WGS

AF:

0.102

AC:

357

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 17, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg464Arg in exon 10 of MYOM1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 25.2% (1026/4068) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11659820). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.34

CADD

Benign

8.8

DANN

Benign

0.59

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

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