22-36295561-A-C

Variant names:

Variant summary

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

The NM_002473.6(MYH9):c.3429T>G(p.Ala1143Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 1,613,802 control chromosomes in the GnomAD database, including 768,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1143A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.97 ( 72088 hom., cov: 30)

Exomes 𝑓: 0.98 ( 695952 hom. )

Consequence

MYH9
NM_002473.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -3.27

Publications

32 publications found

Variant links:

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

MYH9 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 17
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
May-Hegglin anomaly
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH9 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=-0.91).

BP6

Variant 22-36295561-A-C is Benign according to our data. Variant chr22-36295561-A-C is described in ClinVar as Benign. ClinVar VariationId is 44559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. 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
	MYH9	NM_002473.6	MANE Select	c.3429T>G	p.Ala1143Ala	synonymous	Exon 26 of 41	NP_002464.1	P35579-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH9	ENST00000216181.11	TSL:1 MANE Select	c.3429T>G	p.Ala1143Ala	synonymous	Exon 26 of 41	ENSP00000216181.6	P35579-1
MYH9	ENST00000685801.1		c.3492T>G	p.Ala1164Ala	synonymous	Exon 27 of 42	ENSP00000510688.1	A0A8I5KWT8
MYH9	ENST00000955568.1		c.3492T>G	p.Ala1164Ala	synonymous	Exon 27 of 42	ENSP00000625627.1

Frequencies

GnomAD3 genomes

AF:

0.973

AC:

148006

AN:

152072

Hom.:

72020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.995

Gnomad AMR

AF:

0.981

Gnomad ASJ

AF:

0.958

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.984

Gnomad FIN

AF:

0.963

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.972

Gnomad OTH

AF:

0.971

GnomAD2 exomes

AF:

0.977

AC:

245234

AN:

251110

AF XY:

0.977

show subpopulations

Gnomad AFR exome

AF:

0.972

Gnomad AMR exome

AF:

0.987

Gnomad ASJ exome

AF:

0.964

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.961

Gnomad NFE exome

AF:

0.972

Gnomad OTH exome

AF:

0.976

GnomAD4 exome

AF:

0.976

AC:

1426283

AN:

1461612

Hom.:

695952

Cov.:

AF XY:

0.976

AC XY:

709509

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.973

AC:

32562

AN:

33474

American (AMR)

AF:

0.986

AC:

44113

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.961

AC:

25108

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39684

AN:

39700

South Asian (SAS)

AF:

0.985

AC:

84985

AN:

86256

European-Finnish (FIN)

AF:

0.963

AC:

51316

AN:

53308

Middle Eastern (MID)

AF:

0.946

AC:

5345

AN:

5652

European-Non Finnish (NFE)

AF:

0.975

AC:

1084253

AN:

1111994

Other (OTH)

AF:

0.976

AC:

58917

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1988

3976

5963

7951

9939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21658

43316

64974

86632

108290

<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:

0.973

AC:

148134

AN:

152190

Hom.:

72088

Cov.:

AF XY:

0.973

AC XY:

72405

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.971

AC:

40329

AN:

41516

American (AMR)

AF:

0.981

AC:

15004

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

3326

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5166

AN:

5170

South Asian (SAS)

AF:

0.985

AC:

4738

AN:

4812

European-Finnish (FIN)

AF:

0.963

AC:

10198

AN:

10592

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.972

AC:

66138

AN:

68020

Other (OTH)

AF:

0.971

AC:

2049

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

207

415

622

830

1037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.972

Hom.:

100209

Bravo

AF:

0.975

Asia WGS

AF:

0.990

AC:

3443

AN:

3478

EpiCase

AF:

0.973

EpiControl

AF:

0.973

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (3)

Autosomal dominant nonsyndromic hearing loss 17 (2)

Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (1)

MYH9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

(source)

DANN

Benign

0.53

PhyloP100

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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