Genetic Variant MYOM1:c.1501+505G>A (chr18-3163773-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003803.4(MYOM1):c.1501+505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,816 control chromosomes in the GnomAD database, including 10,679 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10679 hom., cov: 32)

Consequence

MYOM1
NM_003803.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.757

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYOM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.1501+505G>A		intron_variant	Intron 10 of 37	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9 link	c.1501+505G>A		intron_variant	Intron 10 of 37	1	NM_003803.4	ENSP00000348821.4		P52179-1
MYOM1	ENST00000261606.11 link	c.1501+505G>A		intron_variant	Intron 10 of 36	1		ENSP00000261606.7		P52179-2

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55986

AN:

151698

Hom.:

10670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.295

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.369

AC:

56031

AN:

151816

Hom.:

10679

Cov.:

AF XY:

0.375

AC XY:

27789

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.445

AC:

18416

AN:

41374

American (AMR)

AF:

0.400

AC:

6108

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1180

AN:

3470

East Asian (EAS)

AF:

0.441

AC:

2271

AN:

5148

South Asian (SAS)

AF:

0.322

AC:

1550

AN:

4814

European-Finnish (FIN)

AF:

0.464

AC:

4871

AN:

10506

Middle Eastern (MID)

AF:

0.290

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.302

AC:

20527

AN:

67908

Other (OTH)

AF:

0.360

AC:

759

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1790

3581

5371

7162

8952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

15222

Bravo

AF:

0.369

Asia WGS

AF:

0.417

AC:

1449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.0

(source)

DANN

Benign

0.82

PhyloP100

-0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over