rs7911700

chr10-25997438-G-A

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.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, single submitter B:1
• Conservation: PhyloP100: -0.110

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=-0.87).
• BP6: Variant 10-25997438-G-A is Benign according to our data. Variant chr10-25997438-G-A is described in ClinVar as [Benign]. Clinvar id is 1250751.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
MYO3A	NM_017433.5	c.508+180G>A		intron_variant		ENST00000642920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3A	ENST00000642920.2	c.508+180G>A		intron_variant			NM_017433.5	P1

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.324

Alfa AF: 0.346 Hom.: 1197

Bravo AF: 0.283

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.6
Dann	Benign	0.77

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: rs7911700; hg19: chr10-26286367;