18-3215232-C-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.-9G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,598,040 control chromosomes in the GnomAD database, including 52,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5726 hom., cov: 32)

Exomes 𝑓: 0.24 ( 47052 hom. )

Consequence

MYOM1
NM_003803.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.601

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=-0.63).

BP6

Variant 18-3215232-C-T is Benign according to our data. Variant chr18-3215232-C-T is described in ClinVar as [Benign]. Clinvar id is 226839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.-9G>A		5_prime_UTR_variant	Exon 2 of 38	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYOM1	ENST00000356443.9 link	c.-9G>A	5_prime_UTR_variant	Exon 2 of 38	1	NM_003803.4	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11 link	c.-9G>A	5_prime_UTR_variant	Exon 2 of 37	1		ENSP00000261606.7	P52179-2
ENSG00000265399	ENST00000580139.1 link	n.198-1760C>T	intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40197

AN:

151996

Hom.:

5731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.324

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.265

AC:

60250

AN:

227484

Hom.:

9207

AF XY:

0.264

AC XY:

32512

AN XY:

123358

show subpopulations

Gnomad AFR exome

AF:

0.292

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.625

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.245

AC:

354050

AN:

1445926

Hom.:

47052

Cov.:

AF XY:

0.245

AC XY:

175749

AN XY:

717178

show subpopulations

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.648

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.264

AC:

40199

AN:

152114

Hom.:

5726

Cov.:

AF XY:

0.267

AC XY:

19873

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.235

Hom.:

4940

Bravo

AF:

0.265

Asia WGS

AF:

0.400

AC:

1392

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

Apr 10, 2019

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

-9G>A in exon 2 of MYOM1: This variant is not expected to have clinical signific ance because it has been identified in 27.9% (1141/4096) of African American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e vs.gs.washington.edu/EVS; dbSNP rs1662315). -

MYOM1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.83

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