12-57037571-T-C

Position:

• chr12-57037571-T-C

Variant summary

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

The ENST00000300119.8(MYO1A):​c.2032A>G​(p.Ile678Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/23 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. I678F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO1A ENST00000300119.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.2032A>G	p.Ile678Val	missense_variant	19/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.2032A>G	p.Ile678Val	missense_variant	20/29		NP_001242970.1
MYO1A	XM_047428876.1	c.2032A>G	p.Ile678Val	missense_variant	20/29		XP_047284832.1
MYO1A	XM_011538373.3	c.2032A>G	p.Ile678Val	missense_variant	19/25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.2032A>G	p.Ile678Val	missense_variant	19/28	1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6	c.2032A>G	p.Ile678Val	missense_variant	20/29	1		ENSP00000393392	P1
MYO1A	ENST00000554234.5	c.1546A>G	p.Ile516Val	missense_variant, NMD_transcript_variant	15/24	5		ENSP00000451033

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.67	N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.18
Sift	Benign	0.16	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0060	B;B
Vest4		0.24
MutPred		0.68		Gain of methylation at K677 (P = 0.0551);Gain of methylation at K677 (P = 0.0551);
MVP		0.64
MPC		0.083
ClinPred		0.34	T
GERP RS		2.6
Varity_R		0.20
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs151269703; hg19: chr12-57431355;