10-26174123-C-T

Variant names:

• chr10-26174123-C-T
• NM_017433.5:c.3859C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2 PM5 BP4_Strong

The NM_017433.5(MYO3A):​c.3859C>T​(p.Pro1287Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1287T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO3A NM_017433.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr10-26174124-C-A is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.05612427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.3859C>T	p.Pro1287Ser	missense_variant	Exon 30 of 35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.3859C>T	p.Pro1287Ser	missense_variant	Exon 30 of 35		NM_017433.5	ENSP00000495965.1
MYO3A	ENST00000543632.5	c.1777-37720C>T		intron_variant	Intron 16 of 16	1		ENSP00000445909.1
MYO3A	ENST00000647478.1	n.*1393+3584C>T		intron_variant	Intron 27 of 29			ENSP00000493932.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 73 AF XY: 0.00 AC XY: 0 AN XY: 727236

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.9
DANN	Benign	0.31
DEOGEN2	Benign	0.079	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.63	.;N
REVEL	Benign	0.093
Sift	Benign	0.065	.;T
Sift4G	Benign	0.43	.;T
Polyphen		0.017	B;B
Vest4		0.20
MutPred		0.12		Gain of MoRF binding (P = 0.0513);Gain of MoRF binding (P = 0.0513);
MVP		0.63
MPC		0.089
ClinPred		0.037	T
GERP RS		1.8
Varity_R		0.045
gMVP		0.13

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: chr10-26463052;