rs6601530

chr8-10813762-G-Achr8-10813762-G-C

Variant summary

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

The NM_017884.6(PINX1):c.471+6431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,890 control chromosomes in the GnomAD database, including 28,663 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 0.60 (28663 hom., cov: 31)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINX1	NM_017884.6	c.471+6431C>T		intron_variant		ENST00000314787.8
PINX1	NM_001284356.2	c.394+12390C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINX1	ENST00000314787.8	c.471+6431C>T		intron_variant		1	NM_017884.6	P2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90980 AN: 151772 Hom.: 28613 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.600 AC: 91085 AN: 151890 Hom.: 28663 Cov.: 31 AF XY: 0.592 AC XY: 43933 AN XY: 74224

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.574

Alfa AF: 0.534 Hom.: 18206

Bravo AF: 0.604

Asia WGS AF: 0.424 AC: 1478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	3.8
Dann	Benign	0.54

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: rs6601530; hg19: chr8-10671272;