Variant chr20-45416197-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015937.6(PIGT):c.41T>G(p.Leu14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIGT
NM_015937.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Variant links:

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 links:

LOC107985405 (HGNC:):

LOC107985405 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGT	NM_015937.6 linkuse as main transcript	c.41T>G	p.Leu14Arg	missense_variant	1/12	ENST00000279036.12	NP_057021.2
LOC107985405	XR_001754640.2 linkuse as main transcript	n.791A>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGT	ENST00000279036.12 linkuse as main transcript	c.41T>G	p.Leu14Arg	missense_variant	1/12	1	NM_015937.6	ENSP00000279036	P1	Q969N2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1438196

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713760

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 19, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.046

T;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.84

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

L;L;L;L;.;.;.;.;.;.;.;.;.;L;.

MutationTaster

Benign

0.68

D;D;D;D;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

N;N;N;N;.;.;.;.;.;.;.;.;N;.;.

REVEL

Benign

0.23

Sift

Uncertain

0.011

D;D;D;D;.;.;.;.;.;.;.;.;T;.;.

Sift4G

Uncertain

0.040

D;D;D;D;.;.;.;.;.;.;.;.;.;.;.

Polyphen

0.44

B;B;.;.;.;.;.;.;.;.;.;.;.;B;.

Vest4

0.75

MutPred

0.83

Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);Gain of methylation at L14 (P = 0.0049);.;

MVP

0.63

MPC

0.18

ClinPred

0.79

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.44

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over