Variant 17-18118725-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016239.4(MYO15A):c.-76A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,597,042 control chromosomes in the GnomAD database, including 124,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17916 hom., cov: 33)

Exomes 𝑓: 0.36 ( 106331 hom. )

Consequence

MYO15A
NM_016239.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-18118725-A-C is Benign according to our data. Variant chr17-18118725-A-C is described in ClinVar as [Benign]. Clinvar id is 322106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO15A	NM_016239.4 link	c.-76A>C		5_prime_UTR_variant	2/66	ENST00000647165.2	NP_057323.3	Q9UKN7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165 link	c.-76A>C		5_prime_UTR_variant	2/66		NM_016239.4	ENSP00000495481.1		Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70059

AN:

151940

Hom.:

17865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.364

AC:

525658

AN:

1444984

Hom.:

106331

Cov.:

AF XY:

0.373

AC XY:

267806

AN XY:

717508

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.502

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.652

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.461

AC:

70164

AN:

152058

Hom.:

17916

Cov.:

AF XY:

0.472

AC XY:

35055

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.650

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.418

Gnomad4 EAS

AF:

0.637

Gnomad4 SAS

AF:

0.706

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.324

Hom.:

2814

Bravo

AF:

0.470

Asia WGS

AF:

0.662

AC:

2300

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.91

CADD

Benign

0.96

DANN

Benign

0.28

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