chr2-46592537-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002643.4(PIGF):ā€‹c.484A>Gā€‹(p.Ser162Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

PIGF
NM_002643.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39
Variant links:
Genes affected
PIGF (HGNC:8962): (phosphatidylinositol glycan anchor biosynthesis class F) This gene encodes a protein involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor, a glycolipid containing three mannose molecules in its core backbone, is found on many blood cells where it serves to anchor proteins to the cell surface. The encoded protein and another GPI synthesis protein, PIGO, function in the transfer of ethanolaminephosphate to the third mannose in GPI. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIGFNM_002643.4 linkuse as main transcriptc.484A>G p.Ser162Gly missense_variant 5/6 ENST00000281382.11 NP_002634.1
PIGFNM_173074.3 linkuse as main transcriptc.484A>G p.Ser162Gly missense_variant 5/7 NP_775097.1
PIGFXM_011532908.4 linkuse as main transcriptc.484A>G p.Ser162Gly missense_variant 5/7 XP_011531210.1
PIGFXM_005264369.4 linkuse as main transcriptc.484A>G p.Ser162Gly missense_variant 5/6 XP_005264426.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIGFENST00000281382.11 linkuse as main transcriptc.484A>G p.Ser162Gly missense_variant 5/61 NM_002643.4 ENSP00000281382 P1Q07326-1
PIGFENST00000306465.8 linkuse as main transcriptc.484A>G p.Ser162Gly missense_variant 5/71 ENSP00000302663 Q07326-2
PIGFENST00000420164.5 linkuse as main transcriptc.94A>G p.Ser32Gly missense_variant, NMD_transcript_variant 2/45 ENSP00000410361
PIGFENST00000412717.1 linkuse as main transcriptc.*53A>G 3_prime_UTR_variant, NMD_transcript_variant 4/53 ENSP00000413202

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251358
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1456522
Hom.:
0
Cov.:
27
AF XY:
0.00000276
AC XY:
2
AN XY:
724990
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:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 22, 2023The c.484A>G (p.S162G) alteration is located in exon 5 (coding exon 4) of the PIGF gene. This alteration results from a A to G substitution at nucleotide position 484, causing the serine (S) at amino acid position 162 to be replaced by a glycine (G). 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
0.17
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.0050
T
MetaRNN
Pathogenic
0.78
D;D
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
1.9
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.16
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.016
D;D
Polyphen
0.97
D;D
Vest4
0.65
MutPred
0.66
Loss of stability (P = 0.0285);Loss of stability (P = 0.0285);
MVP
0.15
MPC
0.017
ClinPred
0.91
D
GERP RS
5.5
Varity_R
0.65
gMVP
0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771621600; hg19: chr2-46819676; API