12-57038505-G-C

Variant names:

• chr12-57038505-G-C
• NM_005379.4:c.1667C>G

Variant summary

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

The NM_005379.4(MYO1A):​c.1667C>G​(p.Ser556Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 5.24

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 rank	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.1667C>G	p.Ser556Cys	missense_variant	Exon 17 of 28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.1667C>G	p.Ser556Cys	missense_variant	Exon 18 of 29		NP_001242970.1
MYO1A	XM_047428876.1	c.1667C>G	p.Ser556Cys	missense_variant	Exon 18 of 29		XP_047284832.1
MYO1A	XM_011538373.3	c.1667C>G	p.Ser556Cys	missense_variant	Exon 17 of 25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.1667C>G	p.Ser556Cys	missense_variant	Exon 17 of 28	1	NM_005379.4	ENSP00000300119.3
MYO1A	ENST00000442789.6	c.1667C>G	p.Ser556Cys	missense_variant	Exon 18 of 29	1		ENSP00000393392.2
MYO1A	ENST00000476795.1	n.564C>G		non_coding_transcript_exon_variant	Exon 3 of 3	5
MYO1A	ENST00000554234.5	n.1181C>G		non_coding_transcript_exon_variant	Exon 13 of 24	5		ENSP00000451033.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.10
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D;D
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;D
Vest4		0.45
MutPred		0.46		Loss of disorder (P = 0.0143);Loss of disorder (P = 0.0143);
MVP		0.95
MPC		0.44
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.70
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr12-57432289;