rs2230162

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003803.4(MYOM1):c.999G>A(p.Gly333Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,590,008 control chromosomes in the GnomAD database, including 75,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6642 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69208 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.828

Publications

14 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

new If you want to explore the variant's impact on the transcript NM_003803.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 18-3176065-C-T is Benign according to our data. Variant chr18-3176065-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.828 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003803.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM1	NM_003803.4	MANE Select	c.999G>A	p.Gly333Gly	synonymous	Exon 6 of 38	NP_003794.3
	MYOM1	NM_019856.2		c.999G>A	p.Gly333Gly	synonymous	Exon 6 of 37	NP_062830.1	P52179-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOM1	ENST00000356443.9	TSL:1 MANE Select	c.999G>A	p.Gly333Gly	synonymous	Exon 6 of 38	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11	TSL:1	c.999G>A	p.Gly333Gly	synonymous	Exon 6 of 37	ENSP00000261606.7	P52179-2
MYOM1	ENST00000941943.1		c.999G>A	p.Gly333Gly	synonymous	Exon 6 of 38	ENSP00000612002.1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44648

AN:

151996

Hom.:

6633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.298

GnomAD2 exomes

AF:

0.282

AC:

69539

AN:

246366

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.306

AC:

440417

AN:

1437894

Hom.:

69208

Cov.:

AF XY:

0.306

AC XY:

219367

AN XY:

716216

show subpopulations

African (AFR)

AF:

0.266

AC:

8779

AN:

32964

American (AMR)

AF:

0.204

AC:

9050

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

8005

AN:

25878

East Asian (EAS)

AF:

0.306

AC:

12074

AN:

39470

South Asian (SAS)

AF:

0.298

AC:

25357

AN:

85000

European-Finnish (FIN)

AF:

0.296

AC:

15724

AN:

53112

Middle Eastern (MID)

AF:

0.229

AC:

1309

AN:

5704

European-Non Finnish (NFE)

AF:

0.314

AC:

342331

AN:

1091864

Other (OTH)

AF:

0.299

AC:

17788

AN:

59548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

12606

25212

37819

50425

63031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11088

22176

33264

44352

55440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.294

AC:

44698

AN:

152114

Hom.:

6642

Cov.:

AF XY:

0.292

AC XY:

21676

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.273

AC:

11324

AN:

41480

American (AMR)

AF:

0.262

AC:

4006

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1083

AN:

3468

East Asian (EAS)

AF:

0.266

AC:

1376

AN:

5168

South Asian (SAS)

AF:

0.304

AC:

1466

AN:

4822

European-Finnish (FIN)

AF:

0.296

AC:

3136

AN:

10582

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.314

AC:

21363

AN:

67992

Other (OTH)

AF:

0.300

AC:

635

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1648

3296

4943

6591

8239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.304

Hom.:

7716

Bravo

AF:

0.288

Asia WGS

AF:

0.285

AC:

990

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.9

(source)

DANN

Benign

0.73

PhyloP100

0.83

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over