Genetic Variant PIN4:c.-21G>T (chrX-72181765-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006223.4(PIN4):c.-21G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,085,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. 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: not found (cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 5 hem. )

Consequence

PIN4
NM_006223.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.734

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16680688).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_006223.4 link	c.-21G>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000373669.8	NP_006214.3	Q9Y237-1
PIN4	NM_001170747.1 link	c.55G>T	p.Val19Phe	missense_variant	Exon 1 of 4		NP_001164218.1	Q9Y237-3
PIN4	NR_033187.2 link	n.9G>T		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.-21G>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_006223.4	ENSP00000362773.3		Q9Y237-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000548

AC:

AN:

182439

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1085604

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

352736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26232

American (AMR)

AF:

0.00

AC:

AN:

35175

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19308

East Asian (EAS)

AF:

0.00

AC:

AN:

30182

South Asian (SAS)

AF:

0.00

AC:

AN:

53789

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3359

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

831411

Other (OTH)

AF:

0.00

AC:

AN:

45634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.4

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.056

T;.;.;T

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.58

.;T;T;.

M_CAP

Benign

0.027

MetaRNN

Benign

0.092

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.73

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.045

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.77

.;.;P;.

Vest4

0.30

MutPred

0.25

Loss of catalytic residue at V19 (P = 0.136);Loss of catalytic residue at V19 (P = 0.136);Loss of catalytic residue at V19 (P = 0.136);.;

MVP

0.14

MPC

0.17

ClinPred

0.30

GERP RS

3.1

PromoterAI

-0.0019

Neutral

(source)

gMVP

0.36

Mutation Taster

=97/3

polymorphism

(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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X-72181765-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over