2-169636543-C-A

Variant names:

• chr2-169636543-C-A
• rs761984175
• NM_004792.3:c.1285C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004792.3(PPIG):​c.1285C>A​(p.His429Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIG NM_004792.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1342127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.1285C>A	p.His429Asn	missense_variant	Exon 14 of 14	ENST00000260970.8	NP_004783.2
PPIG	XM_005246966.3	c.1285C>A	p.His429Asn	missense_variant	Exon 14 of 14		XP_005247023.1
PPIG	XM_005246967.2	c.1285C>A	p.His429Asn	missense_variant	Exon 14 of 14		XP_005247024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.1285C>A	p.His429Asn	missense_variant	Exon 14 of 14	1	NM_004792.3	ENSP00000260970.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.65	.;T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.061
Sift	Uncertain	0.028	D;T;D;D
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.14	B;P;B;B
Vest4		0.40
MutPred		0.38		Gain of relative solvent accessibility (P = 0.0249);.;.;Gain of relative solvent accessibility (P = 0.0249);
MVP		0.28
MPC		0.039
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.075

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

Other links and lift over

dbSNP: rs761984175; hg19: chr2-170493053;