Variant chr2-46615002-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002643.4(PIGF):c.163A>C(p.Asn55His) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,304 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PIGF
NM_002643.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.86

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]

PIGF links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIGF	NM_002643.4 linkuse as main transcript	c.163A>C	p.Asn55His	missense_variant	2/6	ENST00000281382.11	NP_002634.1
PIGF	NM_173074.3 linkuse as main transcript	c.163A>C	p.Asn55His	missense_variant	2/7		NP_775097.1
PIGF	XM_011532908.4 linkuse as main transcript	c.163A>C	p.Asn55His	missense_variant	2/7		XP_011531210.1
PIGF	XM_005264369.4 linkuse as main transcript	c.163A>C	p.Asn55His	missense_variant	2/6		XP_005264426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11 linkuse as main transcript	c.163A>C	p.Asn55His	missense_variant	2/6	1	NM_002643.4	ENSP00000281382	P1	Q07326-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251078

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724886

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.00

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 specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2024

The c.163A>C (p.N55H) alteration is located in exon 2 (coding exon 1) of the PIGF gene. This alteration results from a A to C substitution at nucleotide position 163, causing the asparagine (N) at amino acid position 55 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.052

T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0046

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.17

Sift

Benign

0.25

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.071

B;D

Vest4

0.78

MutPred

0.72

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.26

MPC

0.0068

ClinPred

0.49

GERP RS

5.3

Varity_R

0.32

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over