rs2745061

Variant names:

• chr20-45443556-C-T
• rs2745061
• ENST00000638594.1:c.1485-4688C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638594.1(PIGT):​c.1485-4688C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 151,786 control chromosomes in the GnomAD database, including 1,263 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1263 hom., cov: 32)
• Consequence: PIGT ENST00000638594.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 6 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia

ENSG00000277022 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372631	NR_159957.1	n.351-4041C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGT	ENST00000638594.1	c.1485-4688C>T		intron_variant	Intron 11 of 11	5		ENSP00000491697.1
PIGT	ENST00000424705.3	n.*299-3087C>T		intron_variant	Intron 13 of 14	5		ENSP00000491856.2
ENSG00000277022	ENST00000617473.1	n.1094+3676G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17119 AN: 151700 Hom.: 1261 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17119 AN: 151786 Hom.: 1263 Cov.: 32 AF XY: 0.115 AC XY: 8519 AN XY: 74112

African (AFR) AF: 0.0255 AC: 1055 AN: 41440

American (AMR) AF: 0.174 AC: 2660 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3468

East Asian (EAS) AF: 0.165 AC: 853 AN: 5160

South Asian (SAS) AF: 0.246 AC: 1183 AN: 4808

European-Finnish (FIN) AF: 0.0807 AC: 839 AN: 10396

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9359 AN: 67956

Other (OTH) AF: 0.123 AC: 258 AN: 2094

Alfa AF: 0.135 Hom.: 886

Bravo AF: 0.113

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.71
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs2745061; hg19: chr20-44072196;