NM_003803.4:c.4685+11G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003803.4(MYOM1):c.4685+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,589,660 control chromosomes in the GnomAD database, including 199,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 28410 hom., cov: 33)

Exomes 𝑓: 0.48 ( 171325 hom. )

Consequence

MYOM1
NM_003803.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0300

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 18-3075714-C-A is Benign according to our data. Variant chr18-3075714-C-A is described in ClinVar as [Benign]. Clinvar id is 226826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.4685+11G>T		intron_variant	Intron 35 of 37	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYOM1	ENST00000356443.9 link	c.4685+11G>T	intron_variant	Intron 35 of 37	1	NM_003803.4	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11 link	c.4397+11G>T	intron_variant	Intron 34 of 36	1		ENSP00000261606.7	P52179-2
MYOM1	ENST00000581075.1 link	n.*342G>T	downstream_gene_variant		5		ENSP00000462039.1	J3KRK2

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88404

AN:

151972

Hom.:

28364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.509

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.517

GnomAD3 exomes

AF:

0.492

AC:

113375

AN:

230572

Hom.:

29397

AF XY:

0.491

AC XY:

61116

AN XY:

124470

show subpopulations

Gnomad AFR exome

AF:

0.883

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.497

Gnomad SAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.474

GnomAD4 exome

AF:

0.480

AC:

689856

AN:

1437570

Hom.:

171325

Cov.:

AF XY:

0.481

AC XY:

343684

AN XY:

714240

show subpopulations

Gnomad4 AFR exome

AF:

0.893

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.476

Gnomad4 EAS exome

AF:

0.510

Gnomad4 SAS exome

AF:

0.571

Gnomad4 FIN exome

AF:

0.556

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.502

GnomAD4 genome

AF:

0.582

AC:

88505

AN:

152090

Hom.:

28410

Cov.:

AF XY:

0.582

AC XY:

43223

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.407

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.586

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.474

Hom.:

29949

Bravo

AF:

0.582

Asia WGS

AF:

0.545

AC:

1897

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

4685+11G>T in intron 35 of MYOM1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 46.3% (3809/8224) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs2298539). -

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

-0.89

CADD

Benign

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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