ENST00000592184.1:n.3G>C

Variant names:

• chr19-9835259-G-C
• rs2233681
• ENST00000592184.1:n.3G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 0 publications found

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)

ACMG classification

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
PIN1	NM_006221.4	c.-86G>C		upstream_gene_variant		ENST00000247970.9	NP_006212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9	c.-86G>C		upstream_gene_variant		1	NM_006221.4	ENSP00000247970.5

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

⚠️ 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.

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

Other links and lift over

dbSNP: rs2233681; hg19: chr19-9945935;