12-57038825-C-T

Variant names:

• chr12-57038825-C-T
• NM_005379.4:c.1517G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005379.4(MYO1A):​c.1517G>A​(p.Cys506Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,886 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. C506S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MYO1A NM_005379.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17130122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.1517G>A	p.Cys506Tyr	missense_variant	Exon 16 of 28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.1517G>A	p.Cys506Tyr	missense_variant	Exon 17 of 29		NP_001242970.1
MYO1A	XM_047428876.1	c.1517G>A	p.Cys506Tyr	missense_variant	Exon 17 of 29		XP_047284832.1
MYO1A	XM_011538373.3	c.1517G>A	p.Cys506Tyr	missense_variant	Exon 16 of 25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.1517G>A	p.Cys506Tyr	missense_variant	Exon 16 of 28	1	NM_005379.4	ENSP00000300119.3
MYO1A	ENST00000442789.6	c.1517G>A	p.Cys506Tyr	missense_variant	Exon 17 of 29	1		ENSP00000393392.2
MYO1A	ENST00000476795.1	n.414G>A		non_coding_transcript_exon_variant	Exon 2 of 3	5
MYO1A	ENST00000554234.5	n.1031G>A		non_coding_transcript_exon_variant	Exon 12 of 24	5		ENSP00000451033.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

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: 0.00000360

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	0.091
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.74
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.26	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.59	N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.0	B;B
Vest4		0.24
MutPred		0.36		Gain of methylation at K511 (P = 0.0694);Gain of methylation at K511 (P = 0.0694);
MVP		0.56
MPC		0.14
ClinPred		0.21	T
GERP RS		1.6
Varity_R		0.094
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-57432609;