rs2230162

Positions:

chr18-3176065-C-T

Variant summary

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

The NM_003803.4(MYOM1):c.999G>A(p.Gly333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,590,008 control chromosomes in the GnomAD database, including 75,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6642 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69208 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.828

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 18-3176065-C-T is Benign according to our data. Variant chr18-3176065-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 226838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.828 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOM1	NM_003803.4 linkuse as main transcript	c.999G>A	p.Gly333=	synonymous_variant	6/38	ENST00000356443.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOM1	ENST00000356443.9 linkuse as main transcript	c.999G>A	p.Gly333=	synonymous_variant	6/38	1	NM_003803.4	P2	P52179-1
MYOM1	ENST00000261606.11 linkuse as main transcript	c.999G>A	p.Gly333=	synonymous_variant	6/37	1		A2	P52179-2

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44648

AN:

151996

Hom.:

6633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.282

AC:

69539

AN:

246366

Hom.:

10163

AF XY:

0.286

AC XY:

38184

AN XY:

133618

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.306

AC:

440417

AN:

1437894

Hom.:

69208

Cov.:

AF XY:

0.306

AC XY:

219367

AN XY:

716216

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.294

AC:

44698

AN:

152114

Hom.:

6642

Cov.:

AF XY:

0.292

AC XY:

21676

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.266

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.307

Hom.:

5994

Bravo

AF:

0.288

Asia WGS

AF:

0.285

AC:

990

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

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 17, 2022	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Gly333Gly in exon 6 of MYOM1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 31.2% (2585/8296) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2230162). -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.9

DANN

Benign

0.73

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