rs854772

Positions:

chr17-18151915-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016239.4(MYO15A):c.7857G>A(p.Gly2619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,569,040 control chromosomes in the GnomAD database, including 273,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23974 hom., cov: 32)

Exomes 𝑓: 0.58 ( 249448 hom. )

Consequence

MYO15A
NM_016239.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.101

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:

LOC124903944 (HGNC:):

LOC124903944 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-18151915-G-A is Benign according to our data. Variant chr17-18151915-G-A is described in ClinVar as [Benign]. Clinvar id is 45761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-18151915-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.101 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYO15A	NM_016239.4 linkuse as main transcript	c.7857G>A	p.Gly2619=	synonymous_variant	41/66	ENST00000647165.2
LOC124903944	XR_007065652.1 linkuse as main transcript	n.74-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
MYO15A	XM_017024715.3 linkuse as main transcript	c.7860G>A	p.Gly2620=	synonymous_variant	39/64
MYO15A	XM_017024714.3 linkuse as main transcript	c.7797G>A	p.Gly2599=	synonymous_variant	38/63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO15A	ENST00000647165.2 linkuse as main transcript	c.7857G>A	p.Gly2619=	synonymous_variant	41/66		NM_016239.4	P1	Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83400

AN:

151952

Hom.:

23939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.675

Gnomad EAS

AF:

0.0902

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.565

GnomAD3 exomes

AF:

0.510

AC:

91292

AN:

179054

Hom.:

25410

AF XY:

0.511

AC XY:

48718

AN XY:

95304

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.682

Gnomad EAS exome

AF:

0.0916

Gnomad SAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.584

AC:

827406

AN:

1416970

Hom.:

249448

Cov.:

AF XY:

0.579

AC XY:

405639

AN XY:

700210

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.678

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.582

Gnomad4 NFE exome

AF:

0.621

Gnomad4 OTH exome

AF:

0.564

GnomAD4 genome

AF:

0.549

AC:

83493

AN:

152070

Hom.:

23974

Cov.:

AF XY:

0.537

AC XY:

39943

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.477

Gnomad4 ASJ

AF:

0.675

Gnomad4 EAS

AF:

0.0908

Gnomad4 SAS

AF:

0.391

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.626

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.611

Hom.:

40111

Bravo

AF:

0.541

Asia WGS

AF:

0.278

AC:

967

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Gly2619Gly in Exon 41 of MYO15A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 46.7% (1513/3240) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs854772). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 21, 2016	- -

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.88

DANN

Benign

0.57

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

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