Variant rs2233682 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006221.4(PIN1):c.99G>A(p.Gln33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,609,254 control chromosomes in the GnomAD database, including 1,662 homozygotes. 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 0.061 ( 678 hom., cov: 32)

Exomes 𝑓: 0.016 ( 984 hom. )

Consequence

PIN1
NM_006221.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.745

Variant links:

Genes affected

PIN1 (HGNC:8988): (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) Peptidyl-prolyl cis/trans isomerases (PPIases) catalyze the cis/trans isomerization of peptidyl-prolyl peptide bonds. This gene encodes one of the PPIases, which specifically binds to phosphorylated ser/thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. The conformational regulation catalyzed by this PPIase has a profound impact on key proteins involved in the regulation of cell growth, genotoxic and other stress responses, the immune response, induction and maintenance of pluripotency, germ cell development, neuronal differentiation, and survival. This enzyme also plays a key role in the pathogenesis of Alzheimer's disease and many cancers. Multiple alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jun 2011]

PIN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=0.745 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIN1	NM_006221.4 linkuse as main transcript	c.99G>A	p.Gln33=	synonymous_variant	2/4	ENST00000247970.9	NP_006212.1
PIN1	XM_011528068.3 linkuse as main transcript	c.114G>A	p.Gln38=	synonymous_variant	4/6		XP_011526370.1
PIN1	NR_038422.3 linkuse as main transcript	n.179G>A		non_coding_transcript_exon_variant	3/5
PIN1	NR_038830.2 linkuse as main transcript	n.179G>A		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9 linkuse as main transcript	c.99G>A	p.Gln33=	synonymous_variant	2/4	1	NM_006221.4	ENSP00000247970	P1

Frequencies

GnomAD3 genomes

AF:

0.0613

AC:

9336

AN:

152188

Hom.:

674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0721

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.0370

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00611

Gnomad OTH

AF:

0.0590

GnomAD3 exomes

AF:

0.0372

AC:

8939

AN:

240412

Hom.:

469

AF XY:

0.0321

AC XY:

4181

AN XY:

130386

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.0254

Gnomad SAS exome

AF:

0.0419

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00632

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0162

AC:

23650

AN:

1456948

Hom.:

984

Cov.:

AF XY:

0.0159

AC XY:

11532

AN XY:

724344

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.00512

Gnomad4 OTH exome

AF:

0.0253

GnomAD4 genome

AF:

0.0615

AC:

9363

AN:

152306

Hom.:

678

Cov.:

AF XY:

0.0612

AC XY:

4556

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.0727

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0282

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00613

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0333

Hom.:

197

Bravo

AF:

0.0721

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.0

DANN

Benign

0.68

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

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