chr17-18120828-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016239.4(MYO15A):c.2028C>A(p.Pro676Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,173,212 control chromosomes in the GnomAD database, including 95 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. P676P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0071 ( 3 hom., cov: 32)

Exomes 𝑓: 0.013 ( 92 hom. )

Consequence

MYO15A
NM_016239.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.45

Publications

2 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-18120828-C-A is Benign according to our data. Variant chr17-18120828-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0071 (1048/147518) while in subpopulation NFE AF = 0.0124 (822/66240). AF 95% confidence interval is 0.0117. There are 3 homozygotes in GnomAd4. There are 463 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 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.2028C>A	p.Pro676Pro	synonymous	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.2028C>A	p.Pro676Pro	synonymous	Exon 2 of 66	ENSP00000495481.1	Q9UKN7-1
	MYO15A	ENST00000583079.1	TSL:6	n.1661C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00712

AC:

1049

AN:

147414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00162

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00824

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00493

GnomAD2 exomes

AF:

0.0110

AC:

AN:

2730

AF XY:

0.0128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00568

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0130

AC:

13353

AN:

1025694

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

6348

AN XY:

493742

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

18954

American (AMR)

AF:

0.00242

AC:

AN:

5376

Ashkenazi Jewish (ASJ)

AF:

0.00299

AC:

AN:

10022

East Asian (EAS)

AF:

0.0000656

AC:

AN:

15252

South Asian (SAS)

AF:

0.00208

AC:

AN:

32192

European-Finnish (FIN)

AF:

0.0109

AC:

212

AN:

19420

Middle Eastern (MID)

AF:

0.00327

AC:

AN:

2444

European-Non Finnish (NFE)

AF:

0.0144

AC:

12689

AN:

884192

Other (OTH)

AF:

0.00811

AC:

307

AN:

37842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

858

1716

2574

3432

4290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.00710

AC:

1048

AN:

147518

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

463

AN XY:

71854

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

41084

American (AMR)

AF:

0.00162

AC:

AN:

14858

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00824

AC:

AN:

8740

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0124

AC:

822

AN:

66240

Other (OTH)

AF:

0.00439

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00339

Hom.:

Bravo

AF:

0.00654

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Autosomal recessive nonsyndromic hearing loss 3 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.75

(source)

DANN

Benign

0.74

PhyloP100

-1.4

Mutation Taster

=100/0

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