8-10767344-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017884.6(PINX1):c.472-1428C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,046 control chromosomes in the GnomAD database, including 579 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 0.076 (579 hom., cov: 32)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINX1	NM_017884.6	c.472-1428C>A		intron_variant		ENST00000314787.8
LOC102723313	NR_146188.1	n.341-1056G>T		intron_variant, non_coding_transcript_variant
PINX1	NM_001284356.2	c.395-1428C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINX1	ENST00000314787.8	c.472-1428C>A		intron_variant		1	NM_017884.6	P2
	ENST00000657150.1	n.174-1056G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11519 AN: 151928 Hom.: 579 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0759 AC: 11537 AN: 152046 Hom.: 579 Cov.: 32 AF XY: 0.0753 AC XY: 5599 AN XY: 74316

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0734

Alfa AF: 0.0507 Hom.: 245

Bravo AF: 0.0793

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.057
Dann	Benign	0.19

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: rs13270447; hg19: chr8-10624854;