17-1483016-G-T

Variant names:

• chr17-1483016-G-T
• NM_001080779.2:c.391C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080779.2(MYO1C):​c.391C>A​(p.Arg131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYO1C NM_001080779.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

Genes affected

MYO1C (HGNC:7597): (myosin IC) This gene encodes a member of the unconventional myosin protein family, which are actin-based molecular motors. The protein is found in the cytoplasm, and one isoform with a unique N-terminus is also found in the nucleus. The nuclear isoform associates with RNA polymerase I and II and functions in transcription initiation. The mouse ortholog of this protein also functions in intracellular vesicle transport to the plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. The related gene myosin IE has been referred to as myosin IC in the literature, but it is a distinct locus on chromosome 19. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3090528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1C	NM_001080779.2	c.391C>A	p.Arg131Ser	missense_variant	Exon 4 of 32	ENST00000648651.1	NP_001074248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1C	ENST00000648651.1	c.391C>A	p.Arg131Ser	missense_variant	Exon 4 of 32		NM_001080779.2	ENSP00000496954.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459696 Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1 AN XY: 726202

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Benign	0.80
DEOGEN2	Benign	0.31	.;.;.;T;T;.;.;.;T;T;.;.
Eigen	Benign	0.0040
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.96	.;D;.;.;D;.;.;D;D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.6	.;.;.;L;L;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	.;N;.;.;N;N;.;.;N;.;.;.
REVEL	Uncertain	0.35
Sift	Benign	0.44	.;T;.;.;T;T;.;.;T;.;.;.
Sift4G	Benign	0.42	.;T;T;.;T;T;.;T;T;.;.;.
Polyphen		0.41	B;B;.;P;P;.;.;.;.;.;.;.
Vest4		0.71, 0.68, 0.69, 0.68
MutPred		0.50		.;.;.;Gain of phosphorylation at R131 (P = 0.0266);Gain of phosphorylation at R131 (P = 0.0266);.;.;.;.;.;.;.;
MVP		0.75
MPC		0.65
ClinPred		0.85	D
GERP RS		4.4
Varity_R		0.50
gMVP		0.70

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: chr17-1386310;