rs1261602194

Variant names:

• chr18-62114618-C-A
• rs1261602194
• NM_176787.5:c.1194G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-62114618-C-A
• chr18-62114618-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176787.5(PIGN):​c.1194G>T​(p.Gln398His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,363,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q398Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PIGN NM_176787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• multiple congenital anomalies-hypotonia-seizures syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20025444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.1194G>T	p.Gln398His	missense_variant	Exon 15 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.1194G>T	p.Gln398His	missense_variant	Exon 15 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.1194G>T	p.Gln398His	missense_variant	Exon 14 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.1194G>T		non_coding_transcript_exon_variant	Exon 13 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1363422 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 674476

African (AFR) AF: 0.00 AC: 0 AN: 31022

American (AMR) AF: 0.00 AC: 0 AN: 35466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24922

East Asian (EAS) AF: 0.00 AC: 0 AN: 35472

South Asian (SAS) AF: 0.00 AC: 0 AN: 78172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1047444

Other (OTH) AF: 0.00 AC: 0 AN: 56790

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T;.;T;T;T;.;.;.;.;T;.;.;T;.;T;.;.;.;.;.
Eigen	Benign	0.065
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.93	.;.;.;.;.;.;.;D;D;.;D;D;.;D;D;D;D;.;.;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.1	M;.;M;M;M;.;.;.;.;M;.;.;M;.;M;.;.;.;.;.
PhyloP100		1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	.;.;.;N;.;.;.;.;.;N;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.20
Sift	Benign	0.17	.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.076	.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.
Polyphen		0.94	P;.;P;P;P;.;.;.;.;P;.;.;P;.;P;.;.;.;.;.
Vest4		0.52, 0.52
MutPred		0.42		Loss of MoRF binding (P = 0.119);.;Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);.;Loss of MoRF binding (P = 0.119);.;.;Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);.;Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);Loss of MoRF binding (P = 0.119);
MVP		0.57
MPC		0.14
ClinPred		0.97	D
GERP RS		3.1
Varity_R		0.072
gMVP		0.46
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1261602194; hg19: chr18-59781851;