rs3817419

Variant names:

• chr10-26068891-C-T
• rs3817419
• NM_017433.5:c.1170+7C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017433.5(MYO3A):​c.1170+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,519,798 control chromosomes in the GnomAD database, including 209,500 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17950 hom., cov: 32)
  • Exomes 𝑓: 0.52 (191550 hom.)
• Consequence: MYO3A NM_017433.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002746
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.829

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-26068891-C-T is Benign according to our data. Variant chr10-26068891-C-T is described in ClinVar as [Benign]. Clinvar id is 45798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26068891-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.1170+7C>T		splice_region_variant, intron_variant	Intron 12 of 34	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.1170+7C>T		splice_region_variant, intron_variant	Intron 12 of 34		NM_017433.5	ENSP00000495965.1
MYO3A	ENST00000543632.5	c.1170+7C>T		splice_region_variant, intron_variant	Intron 11 of 16	1		ENSP00000445909.1
MYO3A	ENST00000642197.1	n.1374+7C>T		splice_region_variant, intron_variant	Intron 12 of 26
MYO3A	ENST00000647478.1	n.1170+7C>T		splice_region_variant, intron_variant	Intron 11 of 29			ENSP00000493932.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72155 AN: 151724 Hom.: 17945 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.477

GnomAD3 exomes AF: 0.478 AC: 119792 AN: 250382 Hom.: 30374 AF XY: 0.490 AC XY: 66305 AN XY: 135388

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: 0.524 AC: 716395 AN: 1367956 Hom.: 191550 Cov.: 23 AF XY: 0.524 AC XY: 359402 AN XY: 685498

Gnomad4 AFR exome AF: 0.357

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: 0.548

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.475 AC: 72173 AN: 151842 Hom.: 17950 Cov.: 32 AF XY: 0.475 AC XY: 35234 AN XY: 74216

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.478

Alfa AF: 0.527 Hom.: 7422

Bravo AF: 0.451

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1170+7C>T in Intron 12 of MYO3A: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 45.0% (3162/7020) of European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs3817419). -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 09, 2017

GeneDx

Significance: 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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 30 Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.88
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0
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: rs3817419; hg19: chr10-26357820;