NM_017433.5:c.35A>G

Variant names:

• chr10-25952145-A-G
• NM_017433.5:c.35A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017433.5(MYO3A):​c.35A>G​(p.Asp12Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,042 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO3A NM_017433.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.35A>G	p.Asp12Gly	missense_variant	Exon 3 of 35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.35A>G	p.Asp12Gly	missense_variant	Exon 3 of 35		NM_017433.5	ENSP00000495965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460042 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726396

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.37	N;N;N;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-4.2	.;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0050	.;D;D;D
Sift4G	Uncertain	0.024	.;D;D;D
Polyphen		0.99	D;D;.;D
Vest4		0.26, 0.32, 0.30
MutPred		0.33		Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);
MVP		0.67
MPC		0.094
ClinPred		0.93	D
GERP RS		3.7
Varity_R		0.59
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-26241074;