18-62084578-G-C

Position:

• chr18-62084578-G-C

Variant summary

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

The NM_176787.5(PIGN):​c.2455C>G​(p.Leu819Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000711 in 1,406,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31153893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5	c.2455C>G	p.Leu819Val	missense_variant	27/31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.2455C>G	p.Leu819Val	missense_variant	27/31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.2455C>G	p.Leu819Val	missense_variant	26/30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.*423C>G		non_coding_transcript_exon_variant	25/29	5		ENSP00000491963.1
PIGN	ENST00000638424.1	n.*423C>G		3_prime_UTR_variant	25/29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000711 AC: 10 AN: 1406482 Hom.: 0 Cov.: 28 AF XY: 0.00000720 AC XY: 5 AN XY: 694664

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: 0.00000924

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;.;T;T;T;.;.;.;.;.;T;.;.;T;.;T;.;.
Eigen	Benign	-0.020
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	.;.;.;.;.;.;D;.;D;D;.;D;D;.;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	M;.;M;M;M;.;.;.;.;.;M;.;.;M;.;M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.83	.;.;.;N;.;.;.;.;.;.;N;.;.;.;.;.;.;.
REVEL	Benign	0.24
Sift	Benign	0.24	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.
Sift4G	Benign	0.26	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.
Polyphen		0.99	D;.;D;D;D;.;.;.;.;.;D;.;.;D;.;D;.;.
Vest4		0.41, 0.41
MutPred		0.68		Gain of catalytic residue at L819 (P = 0.083);.;Gain of catalytic residue at L819 (P = 0.083);Gain of catalytic residue at L819 (P = 0.083);Gain of catalytic residue at L819 (P = 0.083);.;.;Gain of catalytic residue at L819 (P = 0.083);.;.;Gain of catalytic residue at L819 (P = 0.083);Gain of catalytic residue at L819 (P = 0.083);.;Gain of catalytic residue at L819 (P = 0.083);.;Gain of catalytic residue at L819 (P = 0.083);Gain of catalytic residue at L819 (P = 0.083);Gain of catalytic residue at L819 (P = 0.083);
MVP		0.60
MPC		0.036
ClinPred		0.70	D
GERP RS		-0.59
Varity_R		0.066
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1190711274; hg19: chr18-59751811;