rs7911700

Variant names:

• chr10-25997438-G-A
• rs7911700
• NM_017433.5:c.508+180G>A

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.508+180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,056 control chromosomes in the GnomAD database, including 7,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.31 (7718 hom., cov: 32)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.110
• Publications: 1 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=-0.87).
• BP6: Variant 10-25997438-G-A is Benign according to our data. Variant chr10-25997438-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.508+180G>A		intron_variant	Intron 6 of 34	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.508+180G>A		intron_variant	Intron 6 of 34		NM_017433.5	ENSP00000495965.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46597 AN: 151936 Hom.: 7721 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46588 AN: 152056 Hom.: 7718 Cov.: 32 AF XY: 0.308 AC XY: 22922 AN XY: 74326

African (AFR) AF: 0.183 AC: 7597 AN: 41474

American (AMR) AF: 0.262 AC: 4003 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1337 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1385 AN: 5190

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4162 AN: 10550

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24970 AN: 67948

Other (OTH) AF: 0.324 AC: 685 AN: 2114

Alfa AF: 0.339 Hom.: 1213

Bravo AF: 0.283

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 21, 2018

GeneDx

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	-0.87
CADD	Benign	3.6
DANN	Benign	0.77
PhyloP100		-0.11
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: rs7911700; hg19: chr10-26286367;