rs202145133

Positions:

chr18-3215085-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003803.4(MYOM1):c.139A>G(p.Ser47Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,613,626 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 61 hom. )

Consequence

MYOM1
NM_003803.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.14

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:

MYOM1 (HGNC:):

MYOM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047293007).

BP6

Variant 18-3215085-T-C is Benign according to our data. Variant chr18-3215085-T-C is described in ClinVar as [Benign]. Clinvar id is 226801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3215085-T-C is described in Lovd as [Likely_pathogenic]. Variant chr18-3215085-T-C is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM1	NM_003803.4 linkuse as main transcript	c.139A>G	p.Ser47Gly	missense_variant	2/38	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYOM1	ENST00000356443.9 linkuse as main transcript	c.139A>G	p.Ser47Gly	missense_variant	2/38	1	NM_003803.4	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11 linkuse as main transcript	c.139A>G	p.Ser47Gly	missense_variant	2/37	1		ENSP00000261606.7	P52179-2
ENSG00000265399	ENST00000580139.1 linkuse as main transcript	n.198-1907T>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1008

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0420

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00663

AC:

1639

AN:

247328

Hom.:

AF XY:

0.00641

AC XY:

863

AN XY:

134668

show subpopulations

Gnomad AFR exome

AF:

0.000722

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.0158

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0372

Gnomad NFE exome

AF:

0.00527

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00618

AC:

9028

AN:

1461326

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

4439

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.0151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0388

Gnomad4 NFE exome

AF:

0.00543

Gnomad4 OTH exome

AF:

0.00731

GnomAD4 genome

AF:

0.00661

AC:

1007

AN:

152300

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000865

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0420

Gnomad4 NFE

AF:

0.00626

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00545

Hom.:

Bravo

AF:

0.00324

ESP6500AA

AF:

0.000983

AC:

ESP6500EA

AF:

0.00251

AC:

ExAC

AF:

0.00529

AC:

640

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00513

EpiControl

AF:

0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Ser47Gly in exon 2 of MYOM1: This variant is not expected to have clinical signi ficance because it has been identified in 4.3% (8/186) of Finnish chromosomes fr om a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/p rojects/SNP; dbSNP rs202145133). -

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 29, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2013

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;.

Eigen

Benign

-0.018

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.052

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.045

D;D

Polyphen

0.20

B;B

Vest4

0.36

MVP

0.78

MPC

0.13

ClinPred

0.0097

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.54

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