dbSNP rs6525589: PIN4:c.-29G>A (chrX-72181757-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006223.4(PIN4):c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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_006223.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

23 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_006223.4 link	c.-29G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000373669.8	NP_006214.3	Q9Y237-1
PIN4	NM_001170747.1 link	c.47G>A	p.Arg16Gln	missense_variant	Exon 1 of 4		NP_001164218.1	Q9Y237-3
PIN4	NR_033187.2 link	n.1G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669.8 link	c.-29G>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_006223.4	ENSP00000362773.3		Q9Y237-1

Frequencies

GnomAD3 genomes

AF:

0.837

AC:

92177

AN:

110095

Hom.:

28291

Cov.:

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

GnomAD2 exomes

AF:

0.863

AC:

157113

AN:

181962

AF XY:

0.868

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 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

African (AFR)

AF:

0.627

AC:

16362

AN:

26116

American (AMR)

AF:

0.851

AC:

29833

AN:

35051

Ashkenazi Jewish (ASJ)

AF:

0.914

AC:

17626

AN:

19286

East Asian (EAS)

AF:

0.526

AC:

15861

AN:

30129

South Asian (SAS)

AF:

0.771

AC:

41456

AN:

53789

European-Finnish (FIN)

AF:

0.939

AC:

38017

AN:

40500

Middle Eastern (MID)

AF:

0.913

AC:

2921

AN:

3201

European-Non Finnish (NFE)

AF:

0.961

AC:

799014

AN:

831101

Other (OTH)

AF:

0.890

AC:

40514

AN:

45539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

2193

4386

6579

8772

10965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20538

41076

61614

82152

102690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.636

AC:

19205

AN:

30191

American (AMR)

AF:

0.834

AC:

8644

AN:

10369

Ashkenazi Jewish (ASJ)

AF:

0.909

AC:

2389

AN:

2627

East Asian (EAS)

AF:

0.517

AC:

1785

AN:

3453

South Asian (SAS)

AF:

0.735

AC:

1915

AN:

2606

European-Finnish (FIN)

AF:

0.943

AC:

5397

AN:

5726

Middle Eastern (MID)

AF:

0.883

AC:

189

AN:

214

European-Non Finnish (NFE)

AF:

0.961

AC:

50721

AN:

52775

Other (OTH)

AF:

0.852

AC:

1283

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

436

871

1307

1742

2178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.910

Hom.:

88386

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-1.1

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.038

(source)

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

PhyloP100

-1.6

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

PromoterAI

-0.029

Neutral

(source)

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over