Genetic Variant PGP:p.Ala21Thr (chr16-2214717-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001042371.3(PGP):c.61G>A(p.Ala21Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,359,632 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PGP
NM_001042371.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0740

Variant links:

Genes affected

PGP (HGNC:8909): (phosphoglycolate phosphatase) Enables glycerol-3-phosphatase activity and phosphoglycolate phosphatase activity. Involved in glycerol biosynthetic process; glycerophospholipid metabolic process; and negative regulation of gluconeogenesis. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PGP links:

Genome browser will be placed here

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=0.07741848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGP	NM_001042371.3 link	c.61G>A	p.Ala21Thr	missense_variant	Exon 1 of 2	ENST00000333503.8	NP_001035830.1	A6NDG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGP	ENST00000333503.8 link	c.61G>A	p.Ala21Thr	missense_variant	Exon 1 of 2	1	NM_001042371.3	ENSP00000330918.7		A6NDG6

Frequencies

GnomAD3 genomes

AF:

0.0000669

AC:

AN:

149546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000625

AC:

AN:

47988

Hom.:

AF XY:

0.0000675

AC XY:

AN XY:

29650

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:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000133

AC:

161

AN:

1210086

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

594442

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:

0.000163

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000669

AC:

AN:

149546

Hom.:

Cov.:

AF XY:

0.0000685

AC XY:

AN XY:

72954

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.61G>A (p.A21T) alteration is located in exon 1 (coding exon 1) of the PGP gene. This alteration results from a G to A substitution at nucleotide position 61, causing the alanine (A) at amino acid position 21 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

0.24

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.070

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.49

REVEL

Benign

0.020

Sift

Benign

0.14

Sift4G

Benign

0.35

Polyphen

0.0020

Vest4

0.13

MVP

0.082

MPC

1.5

ClinPred

0.022

GERP RS

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.059

gMVP

0.37

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