19-9838492-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006221.4(PIN1):c.115G>A(p.Gly39Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,608,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
PIN1
NM_006221.4 missense
NM_006221.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.46
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.17384502).
BS2
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIN1 | NM_006221.4 | c.115G>A | p.Gly39Ser | missense_variant | 2/4 | ENST00000247970.9 | NP_006212.1 | |
PIN1 | XM_011528068.3 | c.130G>A | p.Gly44Ser | missense_variant | 4/6 | XP_011526370.1 | ||
PIN1 | NR_038422.3 | n.195G>A | non_coding_transcript_exon_variant | 3/5 | ||||
PIN1 | NR_038830.2 | n.195G>A | non_coding_transcript_exon_variant | 3/6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000126 AC: 3AN: 238236Hom.: 0 AF XY: 0.00000774 AC XY: 1AN XY: 129212
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1456562Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 724070
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
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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 | Feb 02, 2024 | The c.115G>A (p.G39S) alteration is located in exon 2 (coding exon 2) of the PIN1 gene. This alteration results from a G to A substitution at nucleotide position 115, causing the glycine (G) at amino acid position 39 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.
REVEL
Benign
Sift
Benign
.;D;.
Sift4G
Benign
T;T;T
Polyphen
0.0010
.;B;B
Vest4
MVP
MPC
1.7
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at