4-158715678-C-T

Variant names:

• chr4-158715678-C-T
• rs61756415
• NM_005038.3:c.529G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 789176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005038.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPID	NM_005038.3	MANE Select	c.529G>A	p.Val177Ile	missense	Exon 5 of 10	NP_005029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPID	ENST00000307720.4	TSL:1 MANE Select	c.529G>A	p.Val177Ile	missense	Exon 5 of 10	ENSP00000303754.3
	PPID	ENST00000512699.1	TSL:3	n.43-10G>A		intron	N/A	ENSP00000423207.1

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

GnomAD2 exomes AF: 0.00811 AC: 2038 AN: 251256 AF XY: 0.00826

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 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

African (AFR) AF: 0.00183 AC: 61 AN: 33324

American (AMR) AF: 0.00304 AC: 136 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 370 AN: 26110

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39648

South Asian (SAS) AF: 0.00563 AC: 485 AN: 86144

European-Finnish (FIN) AF: 0.0258 AC: 1377 AN: 53388

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.00887 AC: 9820 AN: 1106746

Other (OTH) AF: 0.00849 AC: 511 AN: 60206

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

African (AFR) AF: 0.00226 AC: 94 AN: 41556

American (AMR) AF: 0.00674 AC: 103 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4822

European-Finnish (FIN) AF: 0.0256 AC: 271 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00970 AC: 660 AN: 68034

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00785 Hom.: 17

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.31
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs61756415; hg19: chr4-159636830; COSMIC: COSV56986997; COSMIC: COSV56986997;