18-62045902-G-T

Position:

• chr18-62045902-G-T

Variant summary

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

The NM_176787.5(PIGN):​c.2750C>A​(p.Thr917Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T917M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.93

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=0.2760245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5	c.2750C>A	p.Thr917Lys	missense_variant	31/31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.2750C>A	p.Thr917Lys	missense_variant	31/31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.2750C>A	p.Thr917Lys	missense_variant	30/30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.*718C>A		non_coding_transcript_exon_variant	29/29	5		ENSP00000491963.1
PIGN	ENST00000638424.1	n.*718C>A		3_prime_UTR_variant	29/29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;.;T;T;T;.;.;.;.;.;T;.;.;T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;.;.;.;.;.;D;.;D;D;.;D;D;.;D;D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.28	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;L;L;.;.;.;.;.;L;.;.;L;.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	.;.;.;N;.;.;.;.;.;.;N;.;.;.;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.018	.;.;.;D;.;.;.;.;.;.;D;.;.;.;.;.
Sift4G	Benign	0.088	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.
Polyphen		0.87	P;.;P;P;P;.;.;.;.;.;P;.;.;P;.;P
Vest4		0.41, 0.41
MutPred		0.32		Gain of MoRF binding (P = 0.0189);.;Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);.;.;.;.;.;Gain of MoRF binding (P = 0.0189);.;.;Gain of MoRF binding (P = 0.0189);.;Gain of MoRF binding (P = 0.0189);
MVP		0.52
MPC		0.053
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.14
gMVP		0.38

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: rs61755364; hg19: chr18-59713135;