10-25952015-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
MYO3A	NM_017433.5	c.-17-79C>T		intron_variant		ENST00000642920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3A	ENST00000642920.2	c.-17-79C>T		intron_variant			NM_017433.5	P1

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6780 AN: 152014 Hom.: 193 Cov.: 32

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

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.: 32 AF XY: 0.0431 AC XY: 3207 AN XY: 74374

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.: 23

Bravo AF: 0.0448

Asia WGS AF: 0.0180 AC: 61 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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

Other links and lift over

dbSNP: rs17450092; hg19: chr10-26240944;