rs3824697

Variant names:

• chr10-26067086-A-G
• rs3824697
• NM_017433.5:c.1053+12A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-26067086-A-G
• chr10-26067086-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017433.5(MYO3A):​c.1053+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,546,196 control chromosomes in the GnomAD database, including 214,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17825 hom., cov: 32)
  • Exomes 𝑓: 0.53 (196863 hom.)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.16
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 30

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal dominant 90

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-26067086-A-G is Benign according to our data. Variant chr10-26067086-A-G is described in ClinVar as Benign. ClinVar VariationId is 45794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.1053+12A>G		intron_variant	Intron 11 of 34	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.1053+12A>G		intron_variant	Intron 11 of 34		NM_017433.5	ENSP00000495965.1
MYO3A	ENST00000543632.5	c.1053+12A>G		intron_variant	Intron 10 of 16	1		ENSP00000445909.1
MYO3A	ENST00000642197.1	n.1257+12A>G		intron_variant	Intron 11 of 26
MYO3A	ENST00000647478.1	n.1053+12A>G		intron_variant	Intron 10 of 29			ENSP00000493932.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71960 AN: 151702 Hom.: 17820 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.477

GnomAD2 exomes AF: 0.477 AC: 118721 AN: 248664 AF XY: 0.489

Gnomad AFR exome AF: 0.352

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.526 AC: 732951 AN: 1394376 Hom.: 196863 Cov.: 24 AF XY: 0.526 AC XY: 366922 AN XY: 697350

African (AFR) AF: 0.357 AC: 11409 AN: 31940

American (AMR) AF: 0.331 AC: 14706 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 13320 AN: 25578

East Asian (EAS) AF: 0.262 AC: 10263 AN: 39210

South Asian (SAS) AF: 0.482 AC: 40769 AN: 84574

European-Finnish (FIN) AF: 0.575 AC: 30487 AN: 53012

Middle Eastern (MID) AF: 0.557 AC: 3125 AN: 5614

European-Non Finnish (NFE) AF: 0.550 AC: 578992 AN: 1051906

Other (OTH) AF: 0.514 AC: 29880 AN: 58156

GnomAD4 genome AF: 0.474 AC: 71978 AN: 151820 Hom.: 17825 Cov.: 32 AF XY: 0.474 AC XY: 35153 AN XY: 74198

African (AFR) AF: 0.359 AC: 14860 AN: 41430

American (AMR) AF: 0.409 AC: 6238 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1402 AN: 5166

South Asian (SAS) AF: 0.493 AC: 2378 AN: 4826

European-Finnish (FIN) AF: 0.578 AC: 6086 AN: 10526

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37597 AN: 67834

Other (OTH) AF: 0.477 AC: 1003 AN: 2102

Alfa AF: 0.518 Hom.: 3734

Bravo AF: 0.451

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 20, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1053+12A>G in Intron 11 of MYO3A: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 46.6% (3270/7020) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs3824697). -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 30 Benign:2

Jan 12, 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. -

Sep 05, 2021

Genome-Nilou Lab

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	-0.84
CADD	Benign	0.89
DANN	Benign	0.44
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3824697; hg19: chr10-26356015; COSMIC: COSV56348765;