chr2-46614975-G-T

Variant summary

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

The NM_002643.4(PIGF):​c.190C>A​(p.Pro64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)

Consequence

PIGF
NM_002643.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
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]

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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=0.23508808).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIGFNM_002643.4 linkuse as main transcriptc.190C>A p.Pro64Thr missense_variant 2/6 ENST00000281382.11 NP_002634.1
PIGFNM_173074.3 linkuse as main transcriptc.190C>A p.Pro64Thr missense_variant 2/7 NP_775097.1
PIGFXM_011532908.4 linkuse as main transcriptc.190C>A p.Pro64Thr missense_variant 2/7 XP_011531210.1
PIGFXM_005264369.4 linkuse as main transcriptc.190C>A p.Pro64Thr missense_variant 2/6 XP_005264426.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIGFENST00000281382.11 linkuse as main transcriptc.190C>A p.Pro64Thr missense_variant 2/61 NM_002643.4 ENSP00000281382 P1Q07326-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 GeneticsAug 13, 2021The c.190C>A (p.P64T) alteration is located in exon 2 (coding exon 1) of the PIGF gene. This alteration results from a C to A substitution at nucleotide position 190, causing the proline (P) at amino acid position 64 to be replaced by a threonine (T). 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
0.092
BayesDel_addAF
Benign
0.0041
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.072
T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.9
L;L
MutationTaster
Benign
0.98
D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.24
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.34
B;D
Vest4
0.30
MutPred
0.54
Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP
0.45
MPC
0.0074
ClinPred
0.77
D
GERP RS
4.4
Varity_R
0.20
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1670561604; hg19: chr2-46842114; API