chr10-26068818-C-T

Position:

chr10-26068818-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_017433.5(MYO3A):c.1104C>T(p.Tyr368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,585,094 control chromosomes in the GnomAD database, including 220,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17865 hom., cov: 33)

Exomes 𝑓: 0.53 ( 202837 hom. )

Consequence

MYO3A
NM_017433.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.123

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 10-26068818-C-T is Benign according to our data. Variant chr10-26068818-C-T is described in ClinVar as [Benign]. Clinvar id is 45796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26068818-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.123 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 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.1104C>T	p.Tyr368=	synonymous_variant	12/35	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.1104C>T	p.Tyr368=	synonymous_variant	12/35		NM_017433.5	ENSP00000495965	P1	Q8NEV4-1
MYO3A	ENST00000543632.5 linkuse as main transcript	c.1104C>T	p.Tyr368=	synonymous_variant	11/17	1		ENSP00000445909
MYO3A	ENST00000642197.1 linkuse as main transcript	n.1308C>T		non_coding_transcript_exon_variant	12/27
MYO3A	ENST00000647478.1 linkuse as main transcript	c.1104C>T	p.Tyr368=	synonymous_variant, NMD_transcript_variant	11/30			ENSP00000493932

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

71993

AN:

151654

Hom.:

17861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.478

AC:

119851

AN:

250570

Hom.:

30357

AF XY:

0.490

AC XY:

66311

AN XY:

135448

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.528

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.579

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.504

GnomAD4 exome

AF:

0.525

AC:

752551

AN:

1433324

Hom.:

202837

Cov.:

AF XY:

0.526

AC XY:

375451

AN XY:

714322

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.330

Gnomad4 ASJ exome

AF:

0.520

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.575

Gnomad4 NFE exome

AF:

0.549

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.474

AC:

72009

AN:

151770

Hom.:

17865

Cov.:

AF XY:

0.474

AC XY:

35133

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.578

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.534

Hom.:

8782

Bravo

AF:

0.451

Asia WGS

AF:

0.397

AC:

1380

AN:

3476

EpiCase

AF:

0.556

EpiControl

AF:

0.560

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Tyr368Tyr in Exon 12 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 49.1% (3446/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35379457). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Autosomal recessive nonsyndromic hearing loss 30

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

2.4

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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