ENST00000380889.6:n.1669A>C

Variant names:

• chr19-9849680-A-C
• rs3178950
• ENST00000380889.6:n.1669A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000380889.6(PIN1):​n.1669A>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIN1 ENST00000380889.6 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 3 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]

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=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380889.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	NM_006221.4	MANE Select	c.*481A>C		3_prime_UTR	Exon 4 of 4	NP_006212.1
	PIN1	NR_038422.3		n.1053A>C		non_coding_transcript_exon	Exon 5 of 5
	PIN1	NR_038830.2		n.722A>C		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	ENST00000380889.6	TSL:1	n.1669A>C		splice_region non_coding_transcript_exon	Exon 6 of 6
	PIN1	ENST00000247970.9	TSL:1 MANE Select	c.*481A>C		3_prime_UTR	Exon 4 of 4	ENSP00000247970.5
	PIN1	ENST00000588695.5	TSL:2	c.*150A>C		splice_region	Exon 5 of 5	ENSP00000466962.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 348952 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 199384

African (AFR) AF: 0.00 AC: 0 AN: 10118

American (AMR) AF: 0.00 AC: 0 AN: 33718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11352

East Asian (EAS) AF: 0.00 AC: 0 AN: 12570

South Asian (SAS) AF: 0.00 AC: 0 AN: 65274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1250

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 182594

Other (OTH) AF: 0.00 AC: 0 AN: 15830

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		0.31

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

Other links and lift over

dbSNP: rs3178950; hg19: chr19-9960356;