chr17-18162574-T-C

Position:

chr17-18162574-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016239.4(MYO15A):c.9518-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,884 control chromosomes in the GnomAD database, including 29,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2871 hom., cov: 33)

Exomes 𝑓: 0.18 ( 26151 hom. )

Consequence

MYO15A
NM_016239.4 intron

Scores

Splicing: ADA: 0.0001856

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.137

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 links:

MYO15A (HGNC:):

MYO15A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-18162574-T-C is Benign according to our data. Variant chr17-18162574-T-C is described in ClinVar as [Benign]. Clinvar id is 45775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-18162574-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYO15A	NM_016239.4 linkuse as main transcript	c.9518-11T>C	intron_variant	ENST00000647165.2	NP_057323.3	Q9UKN7-1
MYO15A	XM_017024715.3 linkuse as main transcript	c.9521-11T>C	intron_variant		XP_016880204.1
MYO15A	XM_017024714.3 linkuse as main transcript	c.9458-11T>C	intron_variant		XP_016880203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2 linkuse as main transcript	c.9518-11T>C		intron_variant			NM_016239.4	ENSP00000495481.1		Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28767

AN:

152100

Hom.:

2857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.00828

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.169

AC:

41433

AN:

245520

Hom.:

3916

AF XY:

0.174

AC XY:

23308

AN XY:

133574

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.00452

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.184

AC:

269281

AN:

1460664

Hom.:

26151

Cov.:

AF XY:

0.186

AC XY:

134874

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.00280

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.189

AC:

28830

AN:

152220

Hom.:

2871

Cov.:

AF XY:

0.184

AC XY:

13705

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.00830

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.197

Hom.:

561

Bravo

AF:

0.193

Asia WGS

AF:

0.108

AC:

374

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	9518-11T>C in Intron 57 of MYO15A: This variant is not expected to have clinical significance because it has been identified in 20.7% (1381/6676) of European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs62073604). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 14, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Autosomal recessive nonsyndromic hearing loss 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

-0.81

CADD

Benign

2.2

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.032

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over