Variant chrX-72181757-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001170747.1(PIN4):c.47G>A(p.Arg16Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.84 ( 28283 hom., 27008 hem., cov: 23)

Exomes 𝑓: 0.92 ( 316946 hom. 325046 hem. )

Failed GnomAD Quality Control

Consequence

PIN4
NM_001170747.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Variant links:

Genes affected

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

PIN4 links:

PIN4 (HGNC:):

PIN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9685785E-6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIN4	NM_006223.4 linkuse as main transcript	c.-29G>A		5_prime_UTR_variant	1/4	ENST00000373669.8	NP_006214.3	Q9Y237-1
PIN4	NM_001170747.1 linkuse as main transcript	c.47G>A	p.Arg16Gln	missense_variant	1/4		NP_001164218.1	Q9Y237-3
PIN4	NR_033187.2 linkuse as main transcript	n.1G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669 linkuse as main transcript	c.-29G>A		5_prime_UTR_variant	1/4	1	NM_006223.4	ENSP00000362773.3		Q9Y237-1

Frequencies

GnomAD3 genomes

AF:

0.837

AC:

92177

AN:

110095

Hom.:

28291

Cov.:

AF XY:

0.831

AC XY:

26962

AN XY:

32457

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.996

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.894

Gnomad NFE

AF:

0.961

Gnomad OTH

AF:

0.851

GnomAD3 exomes

AF:

0.863

AC:

157113

AN:

181962

Hom.:

43884

AF XY:

0.868

AC XY:

57792

AN XY:

66614

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.853

Gnomad ASJ exome

AF:

0.911

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.771

Gnomad FIN exome

AF:

0.937

Gnomad NFE exome

AF:

0.961

Gnomad OTH exome

AF:

0.904

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.923

AC:

1001604

AN:

1084712

Hom.:

316946

Cov.:

AF XY:

0.918

AC XY:

325046

AN XY:

354140

show subpopulations

Gnomad4 AFR exome

AF:

0.627

Gnomad4 AMR exome

AF:

0.851

Gnomad4 ASJ exome

AF:

0.914

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.771

Gnomad4 FIN exome

AF:

0.939

Gnomad4 NFE exome

AF:

0.961

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.837

AC:

92208

AN:

110150

Hom.:

28283

Cov.:

AF XY:

0.830

AC XY:

27008

AN XY:

32522

show subpopulations

Gnomad4 AFR

AF:

0.636

Gnomad4 AMR

AF:

0.834

Gnomad4 ASJ

AF:

0.909

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.735

Gnomad4 FIN

AF:

0.943

Gnomad4 NFE

AF:

0.961

Gnomad4 OTH

AF:

0.852

Alfa

AF:

0.929

Hom.:

84520

Bravo

AF:

0.823

TwinsUK

AF:

0.957

AC:

3549

ALSPAC

AF:

0.954

AC:

2756

ESP6500AA

AF:

0.631

AC:

2418

ESP6500EA

AF:

0.963

AC:

6480

ExAC

AF:

0.860

AC:

104413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-1.1

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.038

DANN

Benign

0.83

DEOGEN2

Benign

0.043

T;.;.

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.32

.;T;T

MetaRNN

Benign

0.0000020

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.015

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.016

MPC

0.12

ClinPred

0.00037

GERP RS

-2.0

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over