chr2-169636766-A-C

Variant names:

• chr2-169636766-A-C
• rs1476635413
• NM_004792.3:c.1508A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004792.3(PPIG):​c.1508A>C​(p.Gln503Pro) 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. 16/22 in silico tools predict 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: 0.305
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041103423).

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.1508A>C	p.Gln503Pro	missense	Exon 14 of 14	NP_004783.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIG	ENST00000260970.8	TSL:1 MANE Select	c.1508A>C	p.Gln503Pro	missense	Exon 14 of 14	ENSP00000260970.3	Q13427-1
	PPIG	ENST00000433207.6	TSL:1	c.1508A>C	p.Gln503Pro	missense	Exon 14 of 15	ENSP00000408683.2	Q13427-1
	PPIG	ENST00000448752.7	TSL:1	c.1508A>C	p.Gln503Pro	missense	Exon 14 of 14	ENSP00000407083.2	Q13427-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.30
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.0060
Sift	Benign	0.21	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.094
MutPred		0.32		Loss of MoRF binding (P = 0.0504)
MVP		0.043
MPC		0.042
ClinPred		0.025	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.021
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1476635413; hg19: chr2-170493276;