Genetic Variant PPIG:p.Arg350Thr (chr2-169636123-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004792.3(PPIG):c.1049G>C(p.Arg350Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,606,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R350K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

PPIG
NM_004792.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.48

Publications

0 publications found

Variant links:

Genes affected

PPIG (HGNC:14650): (peptidylprolyl isomerase G) Enables cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Involved in protein peptidyl-prolyl isomerization. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

PPIG links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004792.3. 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
	PPIG	NM_004792.3	MANE Select	c.1049G>C	p.Arg350Thr	missense	Exon 13 of 14	NP_004783.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPIG	ENST00000260970.8	TSL:1 MANE Select	c.1049G>C	p.Arg350Thr	missense	Exon 13 of 14	ENSP00000260970.3	Q13427-1
PPIG	ENST00000433207.6	TSL:1	c.1049G>C	p.Arg350Thr	missense	Exon 13 of 15	ENSP00000408683.2	Q13427-1
PPIG	ENST00000448752.7	TSL:1	c.1049G>C	p.Arg350Thr	missense	Exon 13 of 14	ENSP00000407083.2	Q13427-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000757

AC:

AN:

1454054

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33014

American (AMR)

AF:

0.00

AC:

AN:

42450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25786

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.00

AC:

AN:

84802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00000992

AC:

AN:

1109382

Other (OTH)

AF:

0.00

AC:

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2088

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

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

0.0080

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.4

PhyloP100

9.5

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-2.0

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.62

MutPred

0.26

Gain of phosphorylation at R350 (P = 4e-04)

MVP

0.25

MPC

1.3

ClinPred

0.91

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.64

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over