rs2230164

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003803.4(MYOM1):c.5040T>C(p.Gly1680Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,602,184 control chromosomes in the GnomAD database, including 198,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25704 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172874 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.491

Publications

18 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 18-3067280-A-G is Benign according to our data. Variant chr18-3067280-A-G is described in ClinVar as Benign. ClinVar VariationId is 226828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.491 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 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.5040T>C	p.Gly1680Gly	synonymous	Exon 38 of 38	NP_003794.3
	MYOM1	NM_019856.2		c.4752T>C	p.Gly1584Gly	synonymous	Exon 37 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.5040T>C	p.Gly1680Gly	synonymous	Exon 38 of 38	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11	TSL:1	c.4752T>C	p.Gly1584Gly	synonymous	Exon 37 of 37	ENSP00000261606.7	P52179-2
MYOM1	ENST00000941943.1		c.5004T>C	p.Gly1668Gly	synonymous	Exon 38 of 38	ENSP00000612002.1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85401

AN:

151940

Hom.:

25666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.501

GnomAD2 exomes

AF:

0.498

AC:

116783

AN:

234312

AF XY:

0.500

show subpopulations

Gnomad AFR exome

AF:

0.788

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.464

Gnomad EAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.469

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.484

AC:

701689

AN:

1450126

Hom.:

172874

Cov.:

AF XY:

0.485

AC XY:

349646

AN XY:

720332

show subpopulations

African (AFR)

AF:

0.799

AC:

26556

AN:

33216

American (AMR)

AF:

0.360

AC:

15562

AN:

43232

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

12156

AN:

25852

East Asian (EAS)

AF:

0.540

AC:

21285

AN:

39384

South Asian (SAS)

AF:

0.567

AC:

48100

AN:

84870

European-Finnish (FIN)

AF:

0.585

AC:

30878

AN:

52744

Middle Eastern (MID)

AF:

0.492

AC:

2034

AN:

4136

European-Non Finnish (NFE)

AF:

0.465

AC:

515114

AN:

1106808

Other (OTH)

AF:

0.501

AC:

30004

AN:

59884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

20625

41250

61874

82499

103124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15514

31028

46542

62056

77570

<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:

0.562

AC:

85495

AN:

152058

Hom.:

25704

Cov.:

AF XY:

0.564

AC XY:

41922

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.790

AC:

32813

AN:

41518

American (AMR)

AF:

0.400

AC:

6105

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1640

AN:

3470

East Asian (EAS)

AF:

0.530

AC:

2733

AN:

5156

South Asian (SAS)

AF:

0.577

AC:

2777

AN:

4810

European-Finnish (FIN)

AF:

0.585

AC:

6170

AN:

10552

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31622

AN:

67974

Other (OTH)

AF:

0.500

AC:

1056

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1814

3628

5442

7256

9070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.473

Hom.:

32582

Bravo

AF:

0.557

Asia WGS

AF:

0.551

AC:

1914

AN:

3478

ClinVar

ClinVar submissions

Significance: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

-0.81

CADD

Benign

0.75

(source)

DANN

Benign

0.19

PhyloP100

-0.49

Mutation Taster

=99/1

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

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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