Genetic Variant PGP:p.Arg228His (chr16-2214011-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001042371.3(PGP):c.683G>A(p.Arg228His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PGP
NM_001042371.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.804

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042371.3. 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
	PGP	NM_001042371.3	MANE Select	c.683G>A	p.Arg228His	missense	Exon 2 of 2	NP_001035830.1	A6NDG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGP	ENST00000333503.8	TSL:1 MANE Select	c.683G>A	p.Arg228His	missense	Exon 2 of 2	ENSP00000330918.7	A6NDG6
	PGP	ENST00000562001.1	TSL:2	n.-113G>A		upstream_gene	N/A	ENSP00000457909.1	H3BV17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000412

AC:

AN:

242492

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1451056

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33254

American (AMR)

AF:

0.00

AC:

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25666

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.00

AC:

AN:

85374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105656

Other (OTH)

AF:

0.00

AC:

AN:

59908

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

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.:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.084

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.59

MutationAssessor

Pathogenic

3.1

PhyloP100

7.7

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.64

MutPred

0.69

Gain of sheet (P = 0.0827)

MVP

0.15

MPC

1.6

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.82

gMVP

0.94

Mutation Taster

=42/58

disease causing

(source)

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

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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