chr19-9835148-A-T

Variant names:

• chr19-9835148-A-T
• rs28589723
• NM_006221.4:c.-197A>T

Variant summary

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

The NM_006221.4(PIN1):​c.-197A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 398,654 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: 0.0000025 (0 hom.)
• Consequence: PIN1 NM_006221.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 2 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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN1	NM_006221.4	c.-197A>T		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.-197A>T		upstream_gene_variant		1	NM_006221.4	ENSP00000247970.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000251 AC: 1 AN: 398654 Hom.: 0 Cov.: 4 AF XY: 0.00000473 AC XY: 1 AN XY: 211496

African (AFR) AF: 0.00 AC: 0 AN: 8148

American (AMR) AF: 0.00 AC: 0 AN: 11560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11608

East Asian (EAS) AF: 0.00 AC: 0 AN: 22988

South Asian (SAS) AF: 0.00 AC: 0 AN: 40136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1740

European-Non Finnish (NFE) AF: 0.00000397 AC: 1 AN: 251854

Other (OTH) AF: 0.00 AC: 0 AN: 22822

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		0.056
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs28589723; hg19: chr19-9945824;