18-3116439-G-C

Position:

chr18-3116439-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003803.4(MYOM1):c.3195C>G(p.Ser1065Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,504 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 24 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.21

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 18-3116439-G-C is Benign according to our data. Variant chr18-3116439-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 239573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000995 (1454/1461242) while in subpopulation AMR AF= 0.0274 (1224/44670). AF 95% confidence interval is 0.0261. There are 24 homozygotes in gnomad4_exome. There are 621 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM1	NM_003803.4 linkuse as main transcript	c.3195C>G	p.Ser1065Ser	synonymous_variant	21/38	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9 linkuse as main transcript	c.3195C>G	p.Ser1065Ser	synonymous_variant	21/38	1	NM_003803.4	ENSP00000348821.4		P52179-1
MYOM1	ENST00000261606.11 linkuse as main transcript	c.2907C>G	p.Ser969Ser	synonymous_variant	20/37	1		ENSP00000261606.7		P52179-2

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

278

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00430

AC:

1069

AN:

248582

Hom.:

AF XY:

0.00317

AC XY:

428

AN XY:

134860

show subpopulations

Gnomad AFR exome

AF:

0.000776

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00173

Gnomad SAS exome

AF:

0.000656

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.0000976

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.000995

AC:

1454

AN:

1461242

Hom.:

Cov.:

AF XY:

0.000854

AC XY:

621

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.000418

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00183

AC:

278

AN:

152262

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ser1065Ser in exon 21 of MYOM1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1.6% (8/492) of Af rican chromosomes from a broad population by the 1000 Genomes Project (http://ww w.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs185366609). -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Mar 04, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.017

DANN

Benign

0.49

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