rs9964300

Positions:

Variant summary

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

The NM_003803.4(MYOM1):c.192G>T(p.Ala64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,612,418 control chromosomes in the GnomAD database, including 3,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 621 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2938 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.711

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=-0.64).

BP6

Variant 18-3215032-C-A is Benign according to our data. Variant chr18-3215032-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 226808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.711 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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.192G>T	p.Ala64=	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.192G>T	p.Ala64=	synonymous_variant	2/38	1	NM_003803.4	ENSP00000348821	P2	P52179-1
MYOM1	ENST00000261606.11 linkuse as main transcript	c.192G>T	p.Ala64=	synonymous_variant	2/37	1		ENSP00000261606	A2	P52179-2
	ENST00000580139.1 linkuse as main transcript	n.198-1960C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0821

AC:

12485

AN:

152136

Hom.:

616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0972

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00695

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.0605

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0626

Gnomad OTH

AF:

0.0732

GnomAD3 exomes

AF:

0.0631

AC:

15468

AN:

245234

Hom.:

598

AF XY:

0.0606

AC XY:

8085

AN XY:

133446

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.0848

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.00684

Gnomad SAS exome

AF:

0.0493

Gnomad FIN exome

AF:

0.0606

Gnomad NFE exome

AF:

0.0640

Gnomad OTH exome

AF:

0.0549

GnomAD4 exome

AF:

0.0604

AC:

88202

AN:

1460164

Hom.:

2938

Cov.:

AF XY:

0.0598

AC XY:

43400

AN XY:

726252

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.0863

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.00766

Gnomad4 SAS exome

AF:

0.0510

Gnomad4 FIN exome

AF:

0.0611

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0578

GnomAD4 genome

AF:

0.0823

AC:

12523

AN:

152254

Hom.:

621

Cov.:

AF XY:

0.0809

AC XY:

6025

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0972

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.00696

Gnomad4 SAS

AF:

0.0481

Gnomad4 FIN

AF:

0.0605

Gnomad4 NFE

AF:

0.0626

Gnomad4 OTH

AF:

0.0724

Alfa

AF:

0.0527

Hom.:

139

Bravo

AF:

0.0841

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.0557

EpiControl

AF:

0.0579

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ala64Ala 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 11.6% (473/4072) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs9964300). -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2019	- -

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

-0.64

CADD

Benign

0.15

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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