rs117612144

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016239.4(MYO15A):c.3026C>A(p.Pro1009His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,612,882 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 67 hom. )

Consequence

MYO15A
NM_016239.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:5

Conservation

PhyloP100: 0.0910

Publications

17 publications found

Variant links:

Genes affected

MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

MYO15A Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO15A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006921023).

BP6

Variant 17-18121826-C-A is Benign according to our data. Variant chr17-18121826-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00373 (568/152306) while in subpopulation EAS AF = 0.0342 (177/5174). AF 95% confidence interval is 0.0301. There are 2 homozygotes in GnomAd4. There are 342 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016239.4. 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
	MYO15A	NM_016239.4	MANE Select	c.3026C>A	p.Pro1009His	missense	Exon 2 of 66	NP_057323.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15A	ENST00000647165.2	MANE Select	c.3026C>A	p.Pro1009His	missense	Exon 2 of 66	ENSP00000495481.1	Q9UKN7-1
	MYO15A	ENST00000583079.1	TSL:6	n.2659C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

567

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0339

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00591

AC:

1466

AN:

247930

AF XY:

0.00568

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.0409

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.00365

GnomAD4 exome

AF:

0.00329

AC:

4807

AN:

1460576

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

2374

AN XY:

726574

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26130

East Asian (EAS)

AF:

0.0470

AC:

1867

AN:

39698

South Asian (SAS)

AF:

0.000556

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0189

AC:

987

AN:

52212

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00155

AC:

1723

AN:

1111946

Other (OTH)

AF:

0.00268

AC:

162

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

346

691

1037

1382

1728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.00373

AC:

568

AN:

152306

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

342

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41568

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0342

AC:

177

AN:

5174

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0216

AC:

229

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00206

AC:

140

AN:

68016

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00324

Hom.:

Bravo

AF:

0.00250

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00613

AC:

740

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00279

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal recessive nonsyndromic hearing loss 3 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.62

MutationAssessor

Benign

2.0

PhyloP100

0.091

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.73

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0050

Polyphen

0.97

Vest4

0.48

MVP

0.68

ClinPred

0.043

GERP RS

0.42

Varity_R

0.14

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(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

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