chr12-57043867-C-G

Position:

• chr12-57043867-C-G

Variant summary

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

The NM_005379.4(MYO1A):​c.881G>C​(p.Arg294Pro) 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 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO1A NM_005379.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

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=0.14313671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.881G>C	p.Arg294Pro	missense_variant	10/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.881G>C	p.Arg294Pro	missense_variant	11/29		NP_001242970.1
MYO1A	XM_047428876.1	c.881G>C	p.Arg294Pro	missense_variant	11/29		XP_047284832.1
MYO1A	XM_011538373.3	c.881G>C	p.Arg294Pro	missense_variant	10/25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.881G>C	p.Arg294Pro	missense_variant	10/28	1	NM_005379.4	ENSP00000300119.3
MYO1A	ENST00000442789.6	c.881G>C	p.Arg294Pro	missense_variant	11/29	1		ENSP00000393392.2
MYO1A	ENST00000492945.5	c.-20-509G>C		intron_variant		4		ENSP00000452229.1
MYO1A	ENST00000554234.5	n.395G>C		non_coding_transcript_exon_variant	6/24	5		ENSP00000451033.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251050 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135696

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.0024	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.42	.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.15	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.14	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.15	B;B
Vest4		0.42
MutPred		0.48		Loss of MoRF binding (P = 0.0594);Loss of MoRF binding (P = 0.0594);
MVP		0.59
MPC		0.15
ClinPred		0.11	T
GERP RS		1.5
Varity_R		0.42
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs368189667; hg19: chr12-57437651;