chr20-45416181-C-G

Variant names:

• chr20-45416181-C-G
• rs750010387
• NM_015937.6:c.25C>G

Variant summary

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

The NM_015937.6(PIGT):​c.25C>G​(p.Leu9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000063 in 1,429,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: PIGT NM_015937.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.97

Genes affected

PIGT (HGNC:14938): (phosphatidylinositol glycan anchor biosynthesis class T) This gene encodes a protein 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 an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

LOC107985405 (HGNC:):

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=0.13919231).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGT	NM_015937.6	c.25C>G	p.Leu9Val	missense_variant	Exon 1 of 12	ENST00000279036.12	NP_057021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGT	ENST00000279036.12	c.25C>G	p.Leu9Val	missense_variant	Exon 1 of 12	1	NM_015937.6	ENSP00000279036.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000154 AC: 3 AN: 194554 Hom.: 0 AF XY: 0.0000188 AC XY: 2 AN XY: 106104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000765

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000630 AC: 9 AN: 1429550 Hom.: 0 Cov.: 31 AF XY: 0.00000564 AC XY: 4 AN XY: 708748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000456

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000835 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0020
DANN	Benign	0.67
DEOGEN2	Benign	0.020	T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.84	T;T;T;T;T;T;T;T;T;T;T;T;T;T;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N;.;.;.;.;.;.;.;.;.;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.29	N;N;N;N;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.036
Sift	Benign	0.73	T;T;T;T;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.27	T;T;T;T;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.0	B;B;.;.;.;.;.;.;.;.;.;.;.;B;.
Vest4		0.20
MutPred		0.69		Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);Gain of catalytic residue at L9 (P = 0.0047);.;
MVP		0.17
MPC		0.12
ClinPred		0.029	T
GERP RS		-5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.032
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs750010387; hg19: chr20-44044821;