Variant chrX-72181801-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006223.4(PIN4):c.16A>G(p.Lys6Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000014 in 1,070,708 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: 0.000014 ( 0 hom. 5 hem. )

Consequence

PIN4
NM_006223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33774433).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIN4	NM_006223.4 linkuse as main transcript	c.16A>G	p.Lys6Glu	missense_variant	1/4	ENST00000373669.8	NP_006214.3	Q9Y237-1
PIN4	NM_001170747.1 linkuse as main transcript	c.91A>G	p.Lys31Glu	missense_variant	1/4		NP_001164218.1	Q9Y237-3
PIN4	NR_033187.2 linkuse as main transcript	n.45A>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.16A>G	p.Lys6Glu	missense_variant	1/4	1	NM_006223.4	ENSP00000362773.3		Q9Y237-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1070708

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

338670

show subpopulations

Gnomad4 AFR exome

AF:

0.0000384

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:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

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

Nov 21, 2024

The c.91A>G (p.K31E) 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 91, causing the lysine (K) at amino acid position 31 to be replaced by a glutamic acid (E). 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

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

T;.;.;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.72

.;T;T;.

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.29

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.047

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.35

MutPred

0.28

Loss of MoRF binding (P = 0.0068);Loss of MoRF binding (P = 0.0068);Loss of MoRF binding (P = 0.0068);.;

MVP

0.59

MPC

0.34

ClinPred

0.96

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.57

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