5-123023946-T-C

Position:

chr5-123023946-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000943.5(PPIC):c.568A>G(p.Asn190Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00075 in 1,614,054 control chromosomes in the GnomAD database, including 1 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N190S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 1 hom. )

Consequence

PPIC
NM_000943.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

PPIC (HGNC:9256): (peptidylprolyl isomerase C) 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. Similar to other PPIases, this protein can bind immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

PPIC links:

SNX24 (HGNC:21533): (sorting nexin 24) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to be involved in protein transport. Predicted to be located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SNX24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03380817).

BP6

Variant 5-123023946-T-C is Benign according to our data. Variant chr5-123023946-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3217187.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIC	NM_000943.5 link	c.568A>G	p.Asn190Asp	missense_variant	5/5	ENST00000306442.5	NP_000934.1	P45877
SNX24	XM_017009395.2 link	c.349-5292T>C		intron_variant			XP_016864884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPIC	ENST00000306442.5 link	c.568A>G	p.Asn190Asp	missense_variant	5/5	1	NM_000943.5	ENSP00000303057.4	P45877
SNX24	ENST00000502387.5 link	n.384-5292T>C		intron_variant		5
SNX24	ENST00000510914.5 link	n.419+1519T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000462

AC:

115

AN:

249044

Hom.:

AF XY:

0.000408

AC XY:

AN XY:

134806

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000826

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000764

AC:

1117

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

527

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000951

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000618

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000749

Hom.:

Bravo

AF:

0.000536

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.82

M_CAP

Benign

0.0058

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.93

PrimateAI

Benign

0.25

PROVEAN

Benign

3.0

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.033

MVP

0.30

MPC

0.17

ClinPred

0.0080

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over