2-169630819-C-G

Variant names:

• chr2-169630819-C-G
• NM_004792.3:c.593C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004792.3(PPIG):​c.593C>G​(p.Ser198Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIG NM_004792.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29381537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.593C>G	p.Ser198Cys	missense_variant	Exon 10 of 14	ENST00000260970.8	NP_004783.2
PPIG	XM_005246966.3	c.593C>G	p.Ser198Cys	missense_variant	Exon 10 of 14		XP_005247023.1
PPIG	XM_005246967.2	c.593C>G	p.Ser198Cys	missense_variant	Exon 10 of 14		XP_005247024.1
PPIG	XM_017005302.3	c.593C>G	p.Ser198Cys	missense_variant	Exon 10 of 12		XP_016860791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.593C>G	p.Ser198Cys	missense_variant	Exon 10 of 14	1	NM_004792.3	ENSP00000260970.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.593C>G (p.S198C) alteration is located in exon 10 (coding exon 8) of the PPIG gene. This alteration results from a C to G substitution at nucleotide position 593, causing the serine (S) at amino acid position 198 to be replaced by a cysteine (C). 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	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T;T;T;.;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	.;T;T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M;.;.;M;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.097
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D;D;T
Polyphen		1.0	D;D;D;D;D;.
Vest4		0.36
MutPred		0.42		Loss of phosphorylation at S198 (P = 0);.;.;Loss of phosphorylation at S198 (P = 0);Loss of phosphorylation at S198 (P = 0);Loss of phosphorylation at S198 (P = 0);
MVP		0.23
MPC		0.89
ClinPred		0.95	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-170487329;