19-9838573-C-G

Variant summary

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

The NM_006221.4(PIN1):ā€‹c.196C>Gā€‹(p.Gln66Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,418,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
Exomes š‘“: 0.0000028 ( 0 hom. )

Consequence

PIN1
NM_006221.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54
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]

Genome browser will be placed here

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=0.13513246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIN1NM_006221.4 linkuse as main transcriptc.196C>G p.Gln66Glu missense_variant 2/4 ENST00000247970.9 NP_006212.1 Q13526
PIN1XM_011528068.3 linkuse as main transcriptc.211C>G p.Gln71Glu missense_variant 4/6 XP_011526370.1
PIN1NR_038422.3 linkuse as main transcriptn.276C>G non_coding_transcript_exon_variant 3/5
PIN1NR_038830.2 linkuse as main transcriptn.276C>G non_coding_transcript_exon_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIN1ENST00000247970.9 linkuse as main transcriptc.196C>G p.Gln66Glu missense_variant 2/41 NM_006221.4 ENSP00000247970.5 Q13526

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000282
AC:
4
AN:
1418742
Hom.:
0
Cov.:
31
AF XY:
0.00000428
AC XY:
3
AN XY:
701512
show subpopulations
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:
0.00000367
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJun 28, 2024The c.196C>G (p.Q66E) alteration is located in exon 2 (coding exon 2) of the PIN1 gene. This alteration results from a C to G substitution at nucleotide position 196, causing the glutamine (Q) at amino acid position 66 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
Benign
0.089
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
22
DANN
Benign
0.94
DEOGEN2
Benign
0.0034
T;T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.019
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;.;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.95
.;N;N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
0.41
.;N;.
REVEL
Benign
0.033
Sift
Benign
0.52
.;T;.
Sift4G
Benign
0.55
T;T;T
Polyphen
0.0
.;B;B
Vest4
0.41
MutPred
0.37
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.69
MPC
0.72
ClinPred
0.82
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-9949249; API