rs370794466

Positions:

• chr18-62113196-C-A
• chr18-62113196-C-T

Variant summary

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

The NM_176787.5(PIGN):​c.1372G>T​(p.Ala458Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 13/21 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)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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 (HGNC:):

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/exons	MANE	Protein	UniProt
PIGN	NM_176787.5	c.1372G>T	p.Ala458Ser	missense_variant	16/31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.1372G>T	p.Ala458Ser	missense_variant	16/31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.1372G>T	p.Ala458Ser	missense_variant	15/30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.1372G>T		non_coding_transcript_exon_variant	14/29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;.;T;T;T;.;.;.;.;T;.;.;T;T;.;.;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	.;.;.;.;.;.;.;D;D;.;D;D;.;D;D;D;.;.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;.;L;L;L;.;.;.;.;L;.;.;L;L;.;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.7	.;.;.;N;.;.;.;.;.;N;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.023	.;.;.;D;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.11	.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.
Polyphen		0.0070	B;.;B;B;B;.;.;.;.;B;.;.;B;B;.;.;.;.;.
Vest4		0.30
MutPred		0.72		Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);.;.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.62
MPC		0.025
ClinPred		0.87	D
GERP RS		4.4
Varity_R		0.083
gMVP		0.28

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: rs370794466; hg19: chr18-59780429;