rs1432217189

Variant names:

• chr20-45416216-G-C
• rs1432217189
• NM_015937.6:c.60G>C

Variant summary

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

The NM_015937.6(PIGT):​c.60G>C​(p.Trp20Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,595,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: PIGT NM_015937.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.692
• Publications: 0 publications found

Genes affected

PIGT (HGNC:14938): (phosphatidylinositol glycan anchor biosynthesis class T) 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 an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

PIGT Gene-Disease associations (from GenCC):

• multiple congenital anomalies-hypotonia-seizures syndrome 3

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

LOC107985405 (HGNC:):

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=0.12765107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015937.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGT	NM_015937.6	MANE Select	c.60G>C	p.Trp20Cys	missense	Exon 1 of 12	NP_057021.2
	PIGT	NM_001184728.3		c.60G>C	p.Trp20Cys	missense	Exon 1 of 11	NP_001171657.1	Q969N2-5
	PIGT	NM_001184729.3		c.60G>C	p.Trp20Cys	missense	Exon 1 of 11	NP_001171658.1	Q969N2-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGT	ENST00000279036.12	TSL:1 MANE Select	c.60G>C	p.Trp20Cys	missense	Exon 1 of 12	ENSP00000279036.6	Q969N2-1
	PIGT	ENST00000372689.9	TSL:1	c.60G>C	p.Trp20Cys	missense	Exon 1 of 11	ENSP00000361774.4	Q969N2-6
	PIGT	ENST00000639382.1	TSL:1	c.60G>C	p.Trp20Cys	missense	Exon 1 of 9	ENSP00000491534.1	A0A1W2PPQ7

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1443098 Hom.: 0 Cov.: 31 AF XY: 0.00000698 AC XY: 5 AN XY: 716402

African (AFR) AF: 0.00 AC: 0 AN: 32992

American (AMR) AF: 0.00 AC: 0 AN: 42032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.00 AC: 0 AN: 38452

South Asian (SAS) AF: 0.00 AC: 0 AN: 83510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00000634 AC: 7 AN: 1103774

Other (OTH) AF: 0.00 AC: 0 AN: 59598

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41480

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.69
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.11
Sift	Benign	0.20	T
Sift4G	Benign	0.18	T
Polyphen		0.23	B
Vest4		0.35
MutPred		0.52		Gain of disorder (P = 0.056)
MVP		0.33
MPC		0.19
ClinPred		0.096	T
GERP RS		3.6
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.56
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1432217189; hg19: chr20-44044856;