rs776294990

Variant names:

• chr1-77154594-C-A
• NM_005482.3:c.841G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-77154594-C-A
• chr1-77154594-C-T

Variant summary

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

The NM_005482.3(PIGK):​c.841G>T​(p.Val281Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. V281M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PIGK NM_005482.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47

Genes affected

PIGK (HGNC:8965): (phosphatidylinositol glycan anchor biosynthesis class K) This gene encodes a member of the cysteine protease family C13 that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is a member of the multisubunit enzyme, GPI transamidase and is thought to be its enzymatic component. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. [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=0.38435405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGK	NM_005482.3	c.841G>T	p.Val281Leu	missense_variant	Exon 9 of 11	ENST00000370812.8	NP_005473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGK	ENST00000370812.8	c.841G>T	p.Val281Leu	missense_variant	Exon 9 of 11	1	NM_005482.3	ENSP00000359848.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460206 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726450

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: 0.00000630

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	0.17
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.0064	T;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.020
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.77	N;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.71	T;T;T
Sift4G	Benign	0.70	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.78
MutPred		0.36		Loss of methylation at K277 (P = 0.1122);.;Loss of methylation at K277 (P = 0.1122);
MVP		0.18
MPC		0.14
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.22
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr1-77620279;