10-26144437-C-T

Position:

• chr10-26144437-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017433.5(MYO3A):​c.2416+836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 150,746 control chromosomes in the GnomAD database, including 13,080 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13080 hom., cov: 28)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.2416+836C>T		intron_variant		ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.2416+836C>T		intron_variant			NM_017433.5	ENSP00000495965.1
MYO3A	ENST00000543632.5	c.1776+47755C>T		intron_variant		1		ENSP00000445909.1
MYO3A	ENST00000642197.1	n.2620+836C>T		intron_variant
MYO3A	ENST00000647478.1	n.*411+836C>T		intron_variant				ENSP00000493932.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62340 AN: 150628 Hom.: 13079 Cov.: 28

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.414 AC: 62370 AN: 150746 Hom.: 13080 Cov.: 28 AF XY: 0.416 AC XY: 30569 AN XY: 73456

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.417

Alfa AF: 0.432 Hom.: 24471

Bravo AF: 0.402

Asia WGS AF: 0.402 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.64

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: rs2096176; hg19: chr10-26433366;