Variant chrX-72181784-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006223.4(PIN4):c.-2A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

PIN4
NM_006223.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12817273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIN4	NM_006223.4 linkuse as main transcript	c.-2A>G		5_prime_UTR_variant	1/4	ENST00000373669.8	NP_006214.3
PIN4	NM_001170747.1 linkuse as main transcript	c.74A>G	p.Lys25Arg	missense_variant	1/4		NP_001164218.1
PIN4	NR_033187.2 linkuse as main transcript	n.28A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669.8 linkuse as main transcript	c.-2A>G		5_prime_UTR_variant	1/4	1	NM_006223.4	ENSP00000362773	P1	Q9Y237-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1085768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352444

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.74A>G (p.K25R) alteration is located in exon 1 (coding exon 1) of the PIN4 gene. This alteration results from a A to G substitution at nucleotide position 74, causing the lysine (K) at amino acid position 25 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.052

T;.;.;T

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.62

.;T;T;.

M_CAP

Benign

0.0094

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.40

N;N;N;N

REVEL

Benign

0.065

Sift

Benign

0.030

D;D;T;D

Sift4G

Uncertain

0.047

D;D;D;D

Polyphen

0.16

.;.;B;.

Vest4

0.094

MutPred

0.16

Loss of ubiquitination at K25 (P = 0.0446);Loss of ubiquitination at K25 (P = 0.0446);Loss of ubiquitination at K25 (P = 0.0446);.;

MVP

0.31

MPC

0.088

ClinPred

0.55

GERP RS

4.1

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over