rs7232679

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_003803.4(MYOM1):c.290+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,561,468 control chromosomes in the GnomAD database, including 62,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7115 hom., cov: 32)

Exomes 𝑓: 0.28 ( 55647 hom. )

Consequence

MYOM1
NM_003803.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.224

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:

ENSG00000265399 (HGNC:):

ENSG00000265399 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=-0.83).

BP6

Variant 18-3214920-G-C is Benign according to our data. Variant chr18-3214920-G-C is described in ClinVar as [Benign]. Clinvar id is 226816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.290+14C>G		intron_variant	Intron 2 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.290+14C>G	intron_variant	Intron 2 of 37	1	NM_003803.4	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11 link	c.290+14C>G	intron_variant	Intron 2 of 36	1		ENSP00000261606.7	P52179-2
ENSG00000265399	ENST00000580139.1 link	n.198-2072G>C	intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45801

AN:

151962

Hom.:

7105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.277

GnomAD3 exomes

AF:

0.272

AC:

57611

AN:

212082

Hom.:

8059

AF XY:

0.270

AC XY:

30905

AN XY:

114396

show subpopulations

Gnomad AFR exome

AF:

0.377

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.205

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.279

AC:

392524

AN:

1409388

Hom.:

55647

Cov.:

AF XY:

0.278

AC XY:

193077

AN XY:

694242

show subpopulations

Gnomad4 AFR exome

AF:

0.374

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.301

AC:

45852

AN:

152080

Hom.:

7115

Cov.:

AF XY:

0.301

AC XY:

22363

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.277

Hom.:

1152

Bravo

AF:

0.296

Asia WGS

AF:

0.279

AC:

970

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

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

- -

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

290+14C>G in intron 2 of MYOM1: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 35.1% (1424/4058) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs7232679). -

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

-0.83

CADD

Benign

1.0

DANN

Benign

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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