chr19-9835259-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000592184.1(PIN1):​n.3G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000906 in 1,103,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

PIN1
ENST00000592184.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

0 publications found
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-DT (HGNC:55303): (PIN1 divergent transcript)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIN1NM_006221.4 linkc.-86G>C upstream_gene_variant ENST00000247970.9 NP_006212.1 Q13526

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIN1ENST00000247970.9 linkc.-86G>C upstream_gene_variant 1 NM_006221.4 ENSP00000247970.5 Q13526

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
9.06e-7
AC:
1
AN:
1103534
Hom.:
0
Cov.:
15
AF XY:
0.00000180
AC XY:
1
AN XY:
555048
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
23044
American (AMR)
AF:
0.00
AC:
0
AN:
32694
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22342
East Asian (EAS)
AF:
0.0000317
AC:
1
AN:
31550
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71534
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33498
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3656
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
837064
Other (OTH)
AF:
0.00
AC:
0
AN:
48152
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.14
DANN
Benign
0.43
PhyloP100
-1.7
PromoterAI
-0.0054
Neutral

Splicing

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

Publications

Other links and lift over

dbSNP: rs2233681; hg19: chr19-9945935; API