rs201397391

Variant names:

• chr18-62045869-C-G
• NM_176787.5:c.2783G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-62045869-C-G
• chr18-62045869-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176787.5(PIGN):​c.2783G>C​(p.Ser928Thr) 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 1,461,502 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S928N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06781036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.2783G>C	p.Ser928Thr	missense_variant	Exon 31 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.2783G>C	p.Ser928Thr	missense_variant	Exon 31 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.2783G>C	p.Ser928Thr	missense_variant	Exon 30 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.*751G>C		non_coding_transcript_exon_variant	Exon 29 of 29	5		ENSP00000491963.1
PIGN	ENST00000638424.1	n.*751G>C		3_prime_UTR_variant	Exon 29 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461502 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727034

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T;.;T;T;T;.;.;.;.;.;T;.;.;T;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.80	.;.;.;.;.;.;T;.;T;T;.;T;T;.;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.068	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;L;L;.;.;.;.;.;L;.;.;L;.;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.62	.;.;.;N;.;.;.;.;.;.;N;.;.;.;.;.
REVEL	Benign	0.022
Sift	Benign	0.70	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.
Sift4G	Benign	0.67	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.
Polyphen		0.12	B;.;B;B;B;.;.;.;.;.;B;.;.;B;.;B
Vest4		0.052, 0.078
MutPred		0.13		Gain of relative solvent accessibility (P = 0.005);.;Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);.;.;.;.;.;Gain of relative solvent accessibility (P = 0.005);.;.;Gain of relative solvent accessibility (P = 0.005);.;Gain of relative solvent accessibility (P = 0.005);
MVP		0.46
MPC		0.023
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.067
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-59713102;