18-62113140-T-G

Variant names:

• chr18-62113140-T-G
• rs182470608
• NM_176787.5:c.1428A>C

Variant summary

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

The NM_176787.5(PIGN):​c.1428A>C​(p.Glu476Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,452,860 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: 0.0000089 (0 hom.)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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=0.065399796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.1428A>C	p.Glu476Asp	missense_variant	Exon 16 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.1428A>C	p.Glu476Asp	missense_variant	Exon 16 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.1428A>C	p.Glu476Asp	missense_variant	Exon 15 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.1428A>C		non_coding_transcript_exon_variant	Exon 14 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000169 AC: 4 AN: 236914 Hom.: 0 AF XY: 0.0000156 AC XY: 2 AN XY: 128160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000895 AC: 13 AN: 1452860 Hom.: 0 Cov.: 29 AF XY: 0.0000125 AC XY: 9 AN XY: 721942

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: 0.000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000249 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.9
DANN	Benign	0.93
DEOGEN2	Benign	0.010	T;.;T;T;T;.;.;.;.;T;.;.;T;T;.;.;.;.;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.70	.;.;.;.;.;.;.;T;T;.;T;T;.;T;T;T;.;.;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.065	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;M;M;M;.;.;.;.;M;.;.;M;M;.;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.30	.;.;.;N;.;.;.;.;.;N;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.026
Sift	Benign	0.31	.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.60	.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.
Polyphen		0.0010	B;.;B;B;B;.;.;.;.;B;.;.;B;B;.;.;.;.;.
Vest4		0.059
MutPred		0.44		Gain of ubiquitination at K471 (P = 0.1008);.;Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);.;Gain of ubiquitination at K471 (P = 0.1008);.;.;Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);.;Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);Gain of ubiquitination at K471 (P = 0.1008);
MVP		0.46
MPC		0.023
ClinPred		0.042	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.14

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: rs182470608; hg19: chr18-59780373;