chr8-10826419-G-C

Position:

• chr8-10826419-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.302-175C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,074 control chromosomes in the GnomAD database, including 15,965 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 0.43 (15965 hom., cov: 33)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINX1	NM_017884.6	c.302-175C>G		intron_variant		ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.302-175C>G		intron_variant			NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.302-175C>G		intron_variant		1	NM_017884.6	ENSP00000318966	P2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65694 AN: 151956 Hom.: 15944 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.432 AC: 65759 AN: 152074 Hom.: 15965 Cov.: 33 AF XY: 0.424 AC XY: 31525 AN XY: 74352

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.432

Alfa AF: 0.345 Hom.: 4874

Bravo AF: 0.442

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.086
DANN	Benign	0.26

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: rs11776767; hg19: chr8-10683929;