Genetic Variant MYO3A:c.-17-79C>T (chr10-25952015-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_017433.5(MYO3A):c.-17-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 1,043,426 control chromosomes in the GnomAD database, including 1,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 194 hom., cov: 32)

Exomes 𝑓: 0.041 ( 921 hom. )

Consequence

MYO3A
NM_017433.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-25952015-C-T is Benign according to our data. Variant chr10-25952015-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 682722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5 link	c.-17-79C>T		intron_variant	Intron 2 of 34	ENST00000642920.2	NP_059129.3	Q8NEV4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 link	c.-17-79C>T		intron_variant	Intron 2 of 34		NM_017433.5	ENSP00000495965.1		Q8NEV4-1

Frequencies

GnomAD3 genomes

AF:

0.0446

AC:

6780

AN:

152014

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0577

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0502

Gnomad OTH

AF:

0.0474

GnomAD4 exome

AF:

0.0410

AC:

36517

AN:

891294

Hom.:

921

AF XY:

0.0410

AC XY:

18715

AN XY:

456752

show subpopulations

Gnomad4 AFR exome

AF:

0.0427

Gnomad4 AMR exome

AF:

0.0281

Gnomad4 ASJ exome

AF:

0.0574

Gnomad4 EAS exome

AF:

0.00122

Gnomad4 SAS exome

AF:

0.0303

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0447

Gnomad4 OTH exome

AF:

0.0409

GnomAD4 genome

AF:

0.0445

AC:

6776

AN:

152132

Hom.:

194

Cov.:

AF XY:

0.0431

AC XY:

3207

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0453

Gnomad4 AMR

AF:

0.0377

Gnomad4 ASJ

AF:

0.0577

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.0385

Gnomad4 NFE

AF:

0.0502

Gnomad4 OTH

AF:

0.0469

Alfa

AF:

0.0481

Hom.:

Bravo

AF:

0.0448

Asia WGS

AF:

0.0180

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.66

DANN

Benign

0.65

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