chr18-62045882-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_176787.5(PIGN):​c.2770G>A​(p.Gly924Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PIGN
NM_176787.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.103866845).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIGNNM_176787.5 linkuse as main transcriptc.2770G>A p.Gly924Ser missense_variant 31/31 ENST00000640252.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIGNENST00000640252.2 linkuse as main transcriptc.2770G>A p.Gly924Ser missense_variant 31/311 NM_176787.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461552
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727054
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 05, 2022The c.2770G>A (p.G924S) alteration is located in exon 31 (coding exon 28) of the PIGN gene. This alteration results from a G to A substitution at nucleotide position 2770, causing the glycine (G) at amino acid position 924 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T;.;T;T;T;.;.;.;.;.;T;.;.;T;.;T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.30
N
LIST_S2
Uncertain
0.92
.;.;.;.;.;.;D;.;D;D;.;D;D;.;D;D
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.10
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;L;L;L;.;.;.;.;.;L;.;.;L;.;L
MutationTaster
Benign
0.71
D;D
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.1
.;.;.;N;.;.;.;.;.;.;N;.;.;.;.;.
REVEL
Benign
0.095
Sift
Benign
0.31
.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.
Sift4G
Benign
0.77
.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.
Polyphen
0.44
B;.;B;B;B;.;.;.;.;.;B;.;.;B;.;B
Vest4
0.30, 0.33
MutPred
0.14
Gain of disorder (P = 0.054);.;Gain of disorder (P = 0.054);Gain of disorder (P = 0.054);Gain of disorder (P = 0.054);.;.;.;.;.;Gain of disorder (P = 0.054);.;.;Gain of disorder (P = 0.054);.;Gain of disorder (P = 0.054);
MVP
0.44
MPC
0.034
ClinPred
0.73
D
GERP RS
5.2
Varity_R
0.078
gMVP
0.29

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.

Other links and lift over

hg19: chr18-59713115; API