Variant 17-18118568-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_016239.4(MYO15A):c.-219-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 595,858 control chromosomes in the GnomAD database, including 60,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 18096 hom., cov: 33)

Exomes 𝑓: 0.41 ( 42793 hom. )

Consequence

MYO15A
NM_016239.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.962

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-18118568-T-C is Benign according to our data. Variant chr17-18118568-T-C is described in ClinVar as [Benign]. Clinvar id is 322102.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 linkuse as main transcript	c.-219-14T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000647165.2	NP_057323.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2 linkuse as main transcript	c.-219-14T>C		splice_polypyrimidine_tract_variant, intron_variant			NM_016239.4	ENSP00000495481	P1	Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70366

AN:

152016

Hom.:

18045

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.413

AC:

183388

AN:

443724

Hom.:

42793

Cov.:

AF XY:

0.428

AC XY:

99513

AN XY:

232494

show subpopulations

Gnomad4 AFR exome

AF:

0.667

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.657

Gnomad4 SAS exome

AF:

0.703

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.463

AC:

70471

AN:

152134

Hom.:

18096

Cov.:

AF XY:

0.473

AC XY:

35186

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.707

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.433

Alfa

AF:

0.374

Hom.:

3596

Bravo

AF:

0.472

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

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

-0.35

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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