17-18135761-C-T

Variant names:

Variant summary

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

The NM_016239.4(MYO15A):c.4533C>T(p.Ala1511Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,614,124 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1511A) has been classified as Likely benign. The gene MYO15A is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.018 ( 57 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 105 hom. )

Consequence

MYO15A
NM_016239.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.77

Publications

3 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

Specifications for MYO15A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 17-18135761-C-T is Benign according to our data. Variant chr17-18135761-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.77 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

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.4533C>T	p.Ala1511Ala	synonymous	Exon 13 of 66	NP_057323.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15A	ENST00000647165.2	MANE Select	c.4533C>T	p.Ala1511Ala	synonymous	Exon 13 of 66	ENSP00000495481.1	Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2758

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.00799

AC:

1991

AN:

249164

AF XY:

0.00746

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.00345

Gnomad ASJ exome

AF:

0.00825

Gnomad EAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.00274

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00611

AC:

8935

AN:

1461848

Hom.:

105

Cov.:

AF XY:

0.00608

AC XY:

4423

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0568

AC:

1903

AN:

33476

American (AMR)

AF:

0.00407

AC:

182

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00838

AC:

219

AN:

26136

East Asian (EAS)

AF:

0.00139

AC:

AN:

39700

South Asian (SAS)

AF:

0.00795

AC:

686

AN:

86256

European-Finnish (FIN)

AF:

0.00238

AC:

127

AN:

53406

Middle Eastern (MID)

AF:

0.0328

AC:

189

AN:

5766

European-Non Finnish (NFE)

AF:

0.00448

AC:

4984

AN:

1111990

Other (OTH)

AF:

0.00977

AC:

590

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

488

975

1463

1950

2438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0183

AC:

2790

AN:

152276

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1354

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0509

AC:

2112

AN:

41532

American (AMR)

AF:

0.00837

AC:

128

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00405

AC:

AN:

5190

South Asian (SAS)

AF:

0.00745

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00565

AC:

384

AN:

68020

Other (OTH)

AF:

0.0189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

271

407

542

678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0135

Hom.:

Bravo

AF:

0.0203

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.00665

EpiControl

AF:

0.00622

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Autosomal recessive nonsyndromic hearing loss 3 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.4

(source)

DANN

Benign

0.67

PhyloP100

-3.8

Mutation Taster

=80/20

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