18-3089524-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003803.4(MYOM1):c.4069+13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,595,004 control chromosomes in the GnomAD database, including 514,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51010 hom., cov: 32)

Exomes 𝑓: 0.80 ( 463129 hom. )

Consequence

MYOM1
NM_003803.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0790

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-3089524-G-T is Benign according to our data. Variant chr18-3089524-G-T is described in ClinVar as Benign. ClinVar VariationId is 226821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 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.4069+13C>A		intron	N/A	NP_003794.3
	MYOM1	NM_019856.2		c.3781+13C>A		intron	N/A	NP_062830.1	P52179-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYOM1	ENST00000356443.9	TSL:1 MANE Select	c.4069+13C>A	intron	N/A	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11	TSL:1	c.3781+13C>A	intron	N/A	ENSP00000261606.7	P52179-2
MYOM1	ENST00000941943.1		c.4033+13C>A	intron	N/A	ENSP00000612002.1

Frequencies

GnomAD3 genomes

AF:

0.819

AC:

124467

AN:

152058

Hom.:

50955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.876

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.755

Gnomad FIN

AF:

0.840

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.821

GnomAD2 exomes

AF:

0.812

AC:

195058

AN:

240184

AF XY:

0.807

show subpopulations

Gnomad AFR exome

AF:

0.835

Gnomad AMR exome

AF:

0.908

Gnomad ASJ exome

AF:

0.836

Gnomad EAS exome

AF:

0.717

Gnomad FIN exome

AF:

0.834

Gnomad NFE exome

AF:

0.799

Gnomad OTH exome

AF:

0.821

GnomAD4 exome

AF:

0.800

AC:

1154821

AN:

1442828

Hom.:

463129

Cov.:

AF XY:

0.800

AC XY:

573775

AN XY:

717158

show subpopulations

African (AFR)

AF:

0.830

AC:

27525

AN:

33152

American (AMR)

AF:

0.904

AC:

39183

AN:

43340

Ashkenazi Jewish (ASJ)

AF:

0.836

AC:

21562

AN:

25792

East Asian (EAS)

AF:

0.752

AC:

29638

AN:

39388

South Asian (SAS)

AF:

0.775

AC:

63873

AN:

82380

European-Finnish (FIN)

AF:

0.834

AC:

42955

AN:

51484

Middle Eastern (MID)

AF:

0.822

AC:

4681

AN:

5694

European-Non Finnish (NFE)

AF:

0.796

AC:

877393

AN:

1101974

Other (OTH)

AF:

0.805

AC:

48011

AN:

59624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

9735

19470

29206

38941

48676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20650

41300

61950

82600

103250

<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:

0.819

AC:

124584

AN:

152176

Hom.:

51010

Cov.:

AF XY:

0.821

AC XY:

61040

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.832

AC:

34546

AN:

41504

American (AMR)

AF:

0.876

AC:

13390

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

2915

AN:

3472

East Asian (EAS)

AF:

0.742

AC:

3853

AN:

5190

South Asian (SAS)

AF:

0.756

AC:

3648

AN:

4824

European-Finnish (FIN)

AF:

0.840

AC:

8890

AN:

10588

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.805

AC:

54735

AN:

68008

Other (OTH)

AF:

0.824

AC:

1733

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1209

2417

3626

4834

6043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.806

Hom.:

202531

Bravo

AF:

0.820

Asia WGS

AF:

0.770

AC:

2677

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypertrophic cardiomyopathy (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.5

(source)

DANN

Benign

0.24

PhyloP100

0.079

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

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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