18-62105586-G-T

Variant names:

• chr18-62105586-G-T
• rs776011686
• NM_176787.5:c.1816C>A

Variant summary

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

The NM_176787.5(PIGN):​c.1816C>A​(p.Pro606Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83

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 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 rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.1816C>A	p.Pro606Thr	missense_variant	Exon 20 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.1816C>A	p.Pro606Thr	missense_variant	Exon 20 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.1816C>A	p.Pro606Thr	missense_variant	Exon 19 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.1816C>A		non_coding_transcript_exon_variant	Exon 18 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000598 AC: 1 AN: 167308 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 88228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000860

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403548 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 692852

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T;.;T;T;T;.;.;.;.;.;T;.;.;T;.;T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	.;.;.;.;.;.;D;.;D;D;.;D;D;.;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.63	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;.;L;L;L;.;.;.;.;.;L;.;.;L;.;L;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	.;.;.;N;.;.;.;.;.;.;N;.;.;.;.;.;.;.
REVEL	Uncertain	0.35
Sift	Benign	0.70	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.
Sift4G	Benign	0.45	.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.
Polyphen		0.99	D;.;D;D;D;.;.;.;.;.;D;.;.;D;.;D;.;.
Vest4		0.79, 0.79
MutPred		0.66		Gain of helix (P = 0.1736);.;Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);.;.;Gain of helix (P = 0.1736);.;.;Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);.;Gain of helix (P = 0.1736);.;Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.73
MPC		0.20
ClinPred		0.73	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.71

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: rs776011686; hg19: chr18-59772819;