chr7-44801307-T-G

Position:

• chr7-44801307-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000468812.6(PPIA):​c.383T>G​(p.Val128Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIA ENST00000468812.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18

Genes affected

PPIA (HGNC:9253): (peptidylprolyl isomerase A) This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIA	NM_021130.5	c.383T>G	p.Val128Gly	missense_variant	5/5	ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2	c.203T>G	p.Val68Gly	missense_variant	6/6		NP_001287910.1
PPIA	XM_047420536.1	c.203T>G	p.Val68Gly	missense_variant	6/6		XP_047276492.1
PPIA	XM_047420537.1	c.203T>G	p.Val68Gly	missense_variant	6/6		XP_047276493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812.6	c.383T>G	p.Val128Gly	missense_variant	5/5	1	NM_021130.5	ENSP00000419425	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.383T>G (p.V128G) alteration is located in exon 5 (coding exon 5) of the PPIA gene. This alteration results from a T to G substitution at nucleotide position 383, causing the valine (V) at amino acid position 128 to be replaced by a glycine (G). 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;.;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.47	T;.;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Pathogenic	4.8	H;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.0	D;D;D;.
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0040	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;.;.;.
Vest4		0.71
MutPred		0.92		Loss of stability (P = 0.0397);.;.;.;
MVP		0.89
MPC		2.9
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.97
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-44840906;