chr17-18141784-G-A

Variant names:

Variant summary

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

The NM_016239.4(MYO15A):c.5649+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,612,992 control chromosomes in the GnomAD database, including 21,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2475 hom., cov: 33)

Exomes 𝑓: 0.14 ( 18993 hom. )

Consequence

MYO15A
NM_016239.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.909

Publications

11 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), PanelApp Australia
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 (BayesDel_noAF=-0.76).

BP6

Variant 17-18141784-G-A is Benign according to our data. Variant chr17-18141784-G-A is described in ClinVar as Benign. ClinVar VariationId is 45750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15A	NM_016239.4 link	c.5649+14G>A		intron_variant	Intron 23 of 65	ENST00000647165.2	NP_057323.3	Q9UKN7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2 link	c.5649+14G>A		intron_variant	Intron 23 of 65		NM_016239.4	ENSP00000495481.1		Q9UKN7-1
MYO15A	ENST00000412324.1 link	n.660+14G>A		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24107

AN:

152060

Hom.:

2468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.186

AC:

46397

AN:

249124

AF XY:

0.175

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.358

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.141

AC:

206290

AN:

1460814

Hom.:

18993

Cov.:

AF XY:

0.140

AC XY:

102074

AN XY:

726754

show subpopulations

African (AFR)

AF:

0.144

AC:

4820

AN:

33462

American (AMR)

AF:

0.344

AC:

15396

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

2999

AN:

26132

East Asian (EAS)

AF:

0.492

AC:

19520

AN:

39682

South Asian (SAS)

AF:

0.153

AC:

13152

AN:

86210

European-Finnish (FIN)

AF:

0.173

AC:

9202

AN:

53210

Middle Eastern (MID)

AF:

0.0853

AC:

492

AN:

5768

European-Non Finnish (NFE)

AF:

0.118

AC:

131205

AN:

1111266

Other (OTH)

AF:

0.157

AC:

9504

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

8827

17655

26482

35310

44137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5150

10300

15450

20600

25750

<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:

0.159

AC:

24124

AN:

152178

Hom.:

2475

Cov.:

AF XY:

0.167

AC XY:

12430

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.148

AC:

6130

AN:

41520

American (AMR)

AF:

0.263

AC:

4017

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

388

AN:

3470

East Asian (EAS)

AF:

0.503

AC:

2597

AN:

5166

South Asian (SAS)

AF:

0.161

AC:

773

AN:

4810

European-Finnish (FIN)

AF:

0.180

AC:

1903

AN:

10588

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7886

AN:

68014

Other (OTH)

AF:

0.158

AC:

333

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

993

1987

2980

3974

4967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.125

Hom.:

2058

Bravo

AF:

0.167

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

5649+14G>A in Intron 23 of MYO15A: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 13.8% (479/3462) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs2072653). -

Autosomal recessive nonsyndromic hearing loss 3

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.0

(source)

DANN

Benign

0.82

PhyloP100

-0.91

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over