chr10-26026402-C-G

Variant names:

• chr10-26026402-C-G
• rs755478240
• NM_017433.5:c.823C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017433.5(MYO3A):​c.823C>G​(p.Arg275Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO3A NM_017433.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.823C>G	p.Arg275Gly	missense_variant	Exon 10 of 35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.823C>G	p.Arg275Gly	missense_variant	Exon 10 of 35		NM_017433.5	ENSP00000495965.1
MYO3A	ENST00000543632.5	c.823C>G	p.Arg275Gly	missense_variant	Exon 9 of 17	1		ENSP00000445909.1
MYO3A	ENST00000642197.1	n.1027C>G		non_coding_transcript_exon_variant	Exon 10 of 27
MYO3A	ENST00000647478.1	n.823C>G		non_coding_transcript_exon_variant	Exon 9 of 30			ENSP00000493932.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T;T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Pathogenic	4.9	H;H;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.7	.;D;D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	.;D;D
Sift4G	Uncertain	0.0070	.;D;D
Polyphen		1.0	D;D;D
Vest4		0.97, 0.96
MutPred		0.83		Loss of ubiquitination at K274 (P = 0.0554);Loss of ubiquitination at K274 (P = 0.0554);Loss of ubiquitination at K274 (P = 0.0554);
MVP		0.84
MPC		0.43
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.96
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs755478240; hg19: chr10-26315331;