rs61756415

Positions:

• chr4-158715678-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005038.3(PPID):​c.529G>A​(p.Val177Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 1,608,334 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0088 (92 hom.)
• Consequence: PPID NM_005038.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.309

Genes affected

PPID (HGNC:9257): (peptidylprolyl isomerase D) The protein encoded by this gene is 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. This protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057251155).
• BP6: Variant 4-158715678-C-T is Benign according to our data. Variant chr4-158715678-C-T is described in ClinVar as [Benign]. Clinvar id is 789176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPID	NM_005038.3	c.529G>A	p.Val177Ile	missense_variant	5/10	ENST00000307720.4
PPID	XM_047415844.1	c.523-10G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPID	ENST00000307720.4	c.529G>A	p.Val177Ile	missense_variant	5/10	1	NM_005038.3	P1
PPID	ENST00000512699.1	c.45-10G>A		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00813 AC: 1237 AN: 152162 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00970

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00811 AC: 2038 AN: 251256 Hom.: 16 AF XY: 0.00826 AC XY: 1122 AN XY: 135804

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00539

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.00875

Gnomad OTH exome AF: 0.00816

GnomAD4 exome AF: 0.00877 AC: 12772 AN: 1456054 Hom.: 92 Cov.: 31 AF XY: 0.00861 AC XY: 6236 AN XY: 724670

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.0142

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00563

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.00887

Gnomad4 OTH exome AF: 0.00849

GnomAD4 genome AF: 0.00812 AC: 1236 AN: 152280 Hom.: 5 Cov.: 33 AF XY: 0.00880 AC XY: 655 AN XY: 74452

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.00674

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.00970

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00818 Hom.: 12

Bravo AF: 0.00625

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.00942 AC: 81

ExAC AF: 0.00796 AC: 966

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00894

EpiControl AF: 0.00788

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.2
DANN	Benign	0.79
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	0.74	D
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.026
Sift	Benign	0.44	T
Sift4G	Benign	0.54	T
Polyphen		0.0050	B
Vest4		0.16
MVP		0.099
MPC		0.14
ClinPred		0.0085	T
GERP RS		-4.3
Varity_R		0.021
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61756415; hg19: chr4-159636830; COSMIC: COSV56986997; COSMIC: COSV56986997;