chr18-3215032-C-A

Variant names:

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.192G>T(p.Ala64Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,612,418 control chromosomes in the GnomAD database, including 3,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 621 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2938 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.711

Publications

6 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:

ENSG00000265399 (HGNC:):

ENSG00000265399 links:

Genome browser will be placed here

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=-0.64).

BP6

Variant 18-3215032-C-A is Benign according to our data. Variant chr18-3215032-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.711 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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.192G>T	p.Ala64Ala	synonymous	Exon 2 of 38	NP_003794.3
	MYOM1	NM_019856.2		c.192G>T	p.Ala64Ala	synonymous	Exon 2 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.192G>T	p.Ala64Ala	synonymous	Exon 2 of 38	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11	TSL:1	c.192G>T	p.Ala64Ala	synonymous	Exon 2 of 37	ENSP00000261606.7	P52179-2
MYOM1	ENST00000941943.1		c.192G>T	p.Ala64Ala	synonymous	Exon 2 of 38	ENSP00000612002.1

Frequencies

GnomAD3 genomes

AF:

0.0821

AC:

12485

AN:

152136

Hom.:

616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0972

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00695

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.0605

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0626

Gnomad OTH

AF:

0.0732

GnomAD2 exomes

AF:

0.0631

AC:

15468

AN:

245234

AF XY:

0.0606

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.0848

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.00684

Gnomad FIN exome

AF:

0.0606

Gnomad NFE exome

AF:

0.0640

Gnomad OTH exome

AF:

0.0549

GnomAD4 exome

AF:

0.0604

AC:

88202

AN:

1460164

Hom.:

2938

Cov.:

AF XY:

0.0598

AC XY:

43400

AN XY:

726252

show subpopulations

African (AFR)

AF:

0.135

AC:

4526

AN:

33444

American (AMR)

AF:

0.0863

AC:

3854

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

640

AN:

26074

East Asian (EAS)

AF:

0.00766

AC:

304

AN:

39668

South Asian (SAS)

AF:

0.0510

AC:

4393

AN:

86150

European-Finnish (FIN)

AF:

0.0611

AC:

3239

AN:

53022

Middle Eastern (MID)

AF:

0.0436

AC:

244

AN:

5594

European-Non Finnish (NFE)

AF:

0.0608

AC:

67518

AN:

1111284

Other (OTH)

AF:

0.0578

AC:

3484

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

4927

9853

14780

19706

24633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2516

5032

7548

10064

12580

<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:

0.0823

AC:

12523

AN:

152254

Hom.:

621

Cov.:

AF XY:

0.0809

AC XY:

6025

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.134

AC:

5580

AN:

41554

American (AMR)

AF:

0.0972

AC:

1486

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

AN:

3470

East Asian (EAS)

AF:

0.00696

AC:

AN:

5170

South Asian (SAS)

AF:

0.0481

AC:

232

AN:

4828

European-Finnish (FIN)

AF:

0.0605

AC:

643

AN:

10620

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0626

AC:

4257

AN:

68006

Other (OTH)

AF:

0.0724

AC:

153

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

581

1163

1744

2326

2907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0556

Hom.:

168

Bravo

AF:

0.0841

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.0557

EpiControl

AF:

0.0579

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

-0.64

CADD

Benign

0.15

(source)

DANN

Benign

0.61

PhyloP100

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over