2-169636198-C-T

Variant names:

• chr2-169636198-C-T
• NM_004792.3:c.1124C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004792.3(PPIG):​c.1124C>T​(p.Ser375Leu) variant causes a missense change. 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: 4.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.1124C>T	p.Ser375Leu	missense_variant	Exon 13 of 14	ENST00000260970.8	NP_004783.2
PPIG	XM_005246966.3	c.1124C>T	p.Ser375Leu	missense_variant	Exon 13 of 14		XP_005247023.1
PPIG	XM_005246967.2	c.1124C>T	p.Ser375Leu	missense_variant	Exon 13 of 14		XP_005247024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.1124C>T	p.Ser375Leu	missense_variant	Exon 13 of 14	1	NM_004792.3	ENSP00000260970.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1124C>T (p.S375L) alteration is located in exon 13 (coding exon 11) of the PPIG gene. This alteration results from a C to T substitution at nucleotide position 1124, causing the serine (S) at amino acid position 375 to be replaced by a leucine (L). 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	0.23
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T;T;T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	.;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L;.;.;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.056
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.043	B;B;B;B
Vest4		0.44
MutPred		0.25		Loss of phosphorylation at S375 (P = 0.0141);.;.;Loss of phosphorylation at S375 (P = 0.0141);
MVP		0.17
MPC		0.82
ClinPred		0.65	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: -5

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: chr2-170492708;