8-10825617-C-T

Position:

• chr8-10825617-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PINX1	NM_017884.6	c.394+535G>A		intron_variant		ENST00000314787.8
PINX1	NM_001284356.2	c.394+535G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINX1	ENST00000314787.8	c.394+535G>A		intron_variant		1	NM_017884.6	P2

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

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.271

Alfa AF: 0.238 Hom.: 2319

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

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

Publications

LitVar

Other links and lift over

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