Genetic Variant PIGF:p.Val117Ile (chr2-46612316-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002643.4(PIGF):c.349G>A(p.Val117Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000766 in 1,304,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V117F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

PIGF
NM_002643.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.22

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

PIGF links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37852708).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002643.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGF	NM_002643.4	MANE Select	c.349G>A	p.Val117Ile	missense	Exon 4 of 6	NP_002634.1	Q6IB04
	PIGF	NM_173074.3		c.349G>A	p.Val117Ile	missense	Exon 4 of 7	NP_775097.1	Q07326-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGF	ENST00000281382.11	TSL:1 MANE Select	c.349G>A	p.Val117Ile	missense	Exon 4 of 6	ENSP00000281382.6	Q07326-1
PIGF	ENST00000306465.8	TSL:1	c.349G>A	p.Val117Ile	missense	Exon 4 of 7	ENSP00000302663.4	Q07326-2
PIGF	ENST00000903157.1		c.349G>A	p.Val117Ile	missense	Exon 4 of 6	ENSP00000573216.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.66e-7

AC:

AN:

1304996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

647228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27268

American (AMR)

AF:

0.00

AC:

AN:

25410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22342

East Asian (EAS)

AF:

0.00

AC:

AN:

33972

South Asian (SAS)

AF:

0.00

AC:

AN:

65390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5250

European-Non Finnish (NFE)

AF:

9.77e-7

AC:

AN:

1023604

Other (OTH)

AF:

0.00

AC:

AN:

53514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

M_CAP

Benign

0.0037

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.2

PhyloP100

4.2

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.15

REVEL

Benign

0.18

Sift

Benign

0.17

Sift4G

Benign

0.071

Polyphen

0.97

Vest4

0.44

MutPred

0.46

Loss of catalytic residue at V117 (P = 0.0911)

MVP

0.34

MPC

0.013

ClinPred

0.68

GERP RS

6.0

Varity_R

0.15

gMVP

0.51

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over