Genetic Variant PIGB:p.Phe524Leu (chr15-55355339-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004855.5(PIGB):c.1572C>G(p.Phe524Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F524F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PIGB
NM_004855.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

0 publications found

Variant links:

Genes affected

PIGB (HGNC:8959): (phosphatidylinositol glycan anchor biosynthesis class B) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases. [provided by RefSeq, Jul 2008]

PIGB links:

CCPG1 (HGNC:24227): (cell cycle progression 1) Involved in positive regulation of cell cycle and positive regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCPG1 links:

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGB	NM_004855.5 link	c.1572C>G	p.Phe524Leu	missense_variant	Exon 12 of 12	ENST00000164305.10	NP_004846.4	Q92521
CCPG1	NM_001204450.2 link	c.*881G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000442196.8	NP_001191379.1	Q9ULG6-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGB	ENST00000164305.10 link	c.1572C>G	p.Phe524Leu	missense_variant	Exon 12 of 12	1	NM_004855.5	ENSP00000164305.5		Q92521
CCPG1	ENST00000442196.8 link	c.*881G>C		3_prime_UTR_variant	Exon 9 of 9	2	NM_001204450.2	ENSP00000403400.3		Q9ULG6-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109532

Other (OTH)

AF:

0.0000166

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.7

H;.

PhyloP100

1.4

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.3

D;.

REVEL

Uncertain

0.40

Sift

Uncertain

0.0080

D;.

Sift4G

Benign

0.14

T;T

Polyphen

0.97

D;.

Vest4

0.78

MutPred

0.77

Gain of helix (P = 0.1736);.;

MVP

0.69

MPC

0.32

ClinPred

0.99

GERP RS

4.2

Varity_R

0.44

gMVP

0.78

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over