rs35575918

Variant names:

• chr19-9849713-A-AG
• rs35575918
• NM_006221.4:c.*514_*515insG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006221.4(PIN1):​c.*514_*515insG variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIN1 NM_006221.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006221.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	NM_006221.4	MANE Select	c.*514_*515insG		downstream_gene	N/A	NP_006212.1	Q13526
	PIN1	NR_038422.3		n.*24_*25insG		downstream_gene	N/A
	PIN1	NR_038830.2		n.*24_*25insG		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	ENST00000247970.9	TSL:1 MANE Select	c.*514_*515insG		downstream_gene	N/A	ENSP00000247970.5	Q13526
	PIN1	ENST00000380889.6	TSL:1	n.*32_*33insG		downstream_gene	N/A
	PIN1	ENST00000929406.1		c.*514_*515insG		downstream_gene	N/A	ENSP00000599465.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs35575918; hg19: chr19-9960389;