rs761984175

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-169636543-C-A
• chr2-169636543-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 in silico tools predict a benign outcome for this variant. 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. H429D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIG NM_004792.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

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

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.1285C>A	p.His429Asn	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.1285C>A	p.His429Asn	missense	Exon 14 of 14	ENSP00000260970.3	Q13427-1
	PPIG	ENST00000433207.6	TSL:1	c.1285C>A	p.His429Asn	missense	Exon 14 of 15	ENSP00000408683.2	Q13427-1
	PPIG	ENST00000448752.7	TSL:1	c.1285C>A	p.His429Asn	missense	Exon 14 of 14	ENSP00000407083.2	Q13427-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.061
Sift	Uncertain	0.028	D
Sift4G	Benign	0.13	T
Polyphen		0.14	B
Vest4		0.40
MutPred		0.38		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
Mutation Taster		=81/19	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: rs761984175; hg19: chr2-170493053;