8-10767344-G-T

Variant names:

• chr8-10767344-G-T
• rs13270447
• NM_017884.6:c.472-1428C>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.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
• Publications: 2 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]

ENSG00000248896 (HGNC:58246):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017884.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	NM_017884.6	MANE Select	c.472-1428C>A		intron	N/A	NP_060354.4
	PINX1	NM_001284356.2		c.395-1428C>A		intron	N/A	NP_001271285.1
	SOX7-AS1	NR_146188.1		n.341-1056G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	ENST00000314787.8	TSL:1 MANE Select	c.472-1428C>A		intron	N/A	ENSP00000318966.3
	PINX1	ENST00000554914.1	TSL:2	c.395-40678C>A		intron	N/A	ENSP00000451145.1
	PINX1	ENST00000519088.5	TSL:1	c.395-1428C>A		intron	N/A	ENSP00000428853.1

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

African (AFR) AF: 0.148 AC: 6112 AN: 41422

American (AMR) AF: 0.0522 AC: 799 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5166

South Asian (SAS) AF: 0.0809 AC: 389 AN: 4806

European-Finnish (FIN) AF: 0.0342 AC: 362 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3349 AN: 67992

Other (OTH) AF: 0.0734 AC: 155 AN: 2112

Alfa AF: 0.0559 Hom.: 389

Bravo AF: 0.0793

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.057
DANN	Benign	0.19
PhyloP100		-0.66
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: rs13270447; hg19: chr8-10624854;