dbSNP rs369249247: PIGN:p.Val698Leu (chr18-62095936-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_176787.5(PIGN):c.2092G>T(p.Val698Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,626 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIGN
NM_176787.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) 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 expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

PIGN links:

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ACMG classification

Classification made for transcript

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=0.117343366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5 link	c.2092G>T	p.Val698Leu	missense_variant	Exon 23 of 31	ENST00000640252.2	NP_789744.1	O95427A0A024R2C3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIGN	ENST00000640252.2 link	c.2092G>T	p.Val698Leu	missense_variant	Exon 23 of 31	1	NM_176787.5	ENSP00000492233.1	O95427
PIGN	ENST00000400334.7 link	c.2092G>T	p.Val698Leu	missense_variant	Exon 22 of 30	1		ENSP00000383188.2	O95427
PIGN	ENST00000638424.1 link	n.2092G>T		non_coding_transcript_exon_variant	Exon 21 of 29	5		ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725328

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.1

DANN

Benign

0.18

DEOGEN2

Benign

0.0096

T;.;T;T;T;.;.;.;.;.;T;.;.;T;.;T;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.87

.;.;.;.;.;.;D;.;D;D;.;D;D;.;D;D;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.040

N;.;N;N;N;.;.;.;.;.;N;.;.;N;.;N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.58

.;.;.;N;.;.;.;.;.;.;N;.;.;.;.;.;.;.

REVEL

Benign

0.082

Sift

Benign

1.0

.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.

Sift4G

Benign

1.0

.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.

Polyphen

0.0010

B;.;B;B;B;.;.;.;.;.;B;.;.;B;.;B;.;.

Vest4

0.11, 0.11

MutPred

0.57

Gain of glycosylation at P699 (P = 0.0654);.;Gain of glycosylation at P699 (P = 0.0654);Gain of glycosylation at P699 (P = 0.0654);Gain of glycosylation at P699 (P = 0.0654);.;.;Gain of glycosylation at P699 (P = 0.0654);.;.;Gain of glycosylation at P699 (P = 0.0654);Gain of glycosylation at P699 (P = 0.0654);.;Gain of glycosylation at P699 (P = 0.0654);.;Gain of glycosylation at P699 (P = 0.0654);Gain of glycosylation at P699 (P = 0.0654);Gain of glycosylation at P699 (P = 0.0654);

MVP

0.43

MPC

0.024

ClinPred

0.024

GERP RS

1.1

Varity_R

0.029

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over