rs12573019

chr10-26025376-G-A

Variant summary

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

The NM_017433.5(MYO3A):c.798-1001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 150,428 control chromosomes in the GnomAD database, including 1,625 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 0.13 (1625 hom., cov: 31)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3A	NM_017433.5	c.798-1001G>A		intron_variant		ENST00000642920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3A	ENST00000642920.2	c.798-1001G>A		intron_variant			NM_017433.5	P1
MYO3A	ENST00000543632.5	c.798-1001G>A		intron_variant		1
MYO3A	ENST00000647478.1	c.798-1001G>A		intron_variant, NMD_transcript_variant
MYO3A	ENST00000642197.1	n.1002-1001G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.126 AC: 18875 AN: 150310 Hom.: 1620 Cov.: 31

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.126 AC: 18881 AN: 150428 Hom.: 1625 Cov.: 31 AF XY: 0.131 AC XY: 9644 AN XY: 73398

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.133

Alfa AF: 0.139 Hom.: 2071

Bravo AF: 0.123

Asia WGS AF: 0.239 AC: 831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.037
Dann	Benign	0.49

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: rs12573019; hg19: chr10-26314305;