8-10825617-C-T

Variant names:

• chr8-10825617-C-T
• rs7840785
• NM_017884.6:c.394+535G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017884.6(PINX1):​c.394+535G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,116 control chromosomes in the GnomAD database, including 4,333 homozygotes. 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: 𝑓 0.23 (4333 hom., cov: 32)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65
• Publications: 7 publications found

Genes affected

PINX1 (HGNC:30046): (PIN2 (TERF1) interacting telomerase inhibitor 1) Enables telomerase RNA binding activity and telomerase inhibitor activity. Involved in several processes, including negative regulation of DNA biosynthetic process; positive regulation of protein localization to nucleolus; and protein localization to organelle. Acts upstream of or within telomere maintenance via telomerase. Located in several cellular components, including chromosomal region; nuclear lumen; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

MIR1322 (HGNC:35374): (microRNA 1322) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINX1	NM_017884.6	c.394+535G>A		intron_variant	Intron 5 of 6	ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.394+535G>A		intron_variant	Intron 5 of 5		NP_001271285.1
MIR1322	NR_031711.1	n.-174G>A		upstream_gene_variant
MIR1322	unassigned_transcript_1451	n.-224G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.394+535G>A		intron_variant	Intron 5 of 6	1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.394+535G>A		intron_variant	Intron 5 of 5	2		ENSP00000451145.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35689 AN: 152000 Hom.: 4333 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35694 AN: 152116 Hom.: 4333 Cov.: 32 AF XY: 0.230 AC XY: 17074 AN XY: 74368

African (AFR) AF: 0.194 AC: 8045 AN: 41506

American (AMR) AF: 0.199 AC: 3038 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3472

East Asian (EAS) AF: 0.172 AC: 889 AN: 5170

South Asian (SAS) AF: 0.198 AC: 955 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2393 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18536 AN: 67980

Other (OTH) AF: 0.271 AC: 571 AN: 2110

Alfa AF: 0.242 Hom.: 2635

Bravo AF: 0.231

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.74
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs7840785; hg19: chr8-10683127; COSMIC: COSV59110739; COSMIC: COSV59110739;