10-25997230-G-T

Position:

chr10-25997230-G-T

Variant summary

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

The NM_017433.5(MYO3A):c.480G>T(p.Thr160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,612,676 control chromosomes in the GnomAD database, including 3,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 1226 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2535 hom. )

Consequence

MYO3A
NM_017433.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.91

Variant links:

Genes affected

MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

MYO3A 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=-0.8).

BP6

Variant 10-25997230-G-T is Benign according to our data. Variant chr10-25997230-G-T is described in ClinVar as [Benign]. Clinvar id is 45817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5 linkuse as main transcript	c.480G>T	p.Thr160=	synonymous_variant	6/35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 linkuse as main transcript	c.480G>T	p.Thr160=	synonymous_variant	6/35		NM_017433.5	ENSP00000495965	P1	Q8NEV4-1

Frequencies

GnomAD3 genomes

AF:

0.0951

AC:

14455

AN:

152034

Hom.:

1219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0664

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0835

GnomAD3 exomes

AF:

0.0542

AC:

13596

AN:

250992

Hom.:

658

AF XY:

0.0517

AC XY:

7015

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0364

Gnomad ASJ exome

AF:

0.0575

Gnomad EAS exome

AF:

0.00261

Gnomad SAS exome

AF:

0.0315

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0541

Gnomad OTH exome

AF:

0.0495

GnomAD4 exome

AF:

0.0494

AC:

72135

AN:

1460526

Hom.:

2535

Cov.:

AF XY:

0.0487

AC XY:

35363

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0394

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.0312

Gnomad4 FIN exome

AF:

0.0360

Gnomad4 NFE exome

AF:

0.0478

Gnomad4 OTH exome

AF:

0.0536

GnomAD4 genome

AF:

0.0952

AC:

14486

AN:

152150

Hom.:

1226

Cov.:

AF XY:

0.0932

AC XY:

6931

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.0663

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0826

Alfa

AF:

0.0592

Hom.:

494

Bravo

AF:

0.102

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Thr160Thr in Exon 06 of MYO3A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 21.5% (802/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs12257119). -
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	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 30

Benign:1

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

-0.80

CADD

Benign

0.090

DANN

Benign

0.35

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