chr8-10785654-C-T

Variant names:

• chr8-10785654-C-T
• rs9657541
• NM_017884.6:c.472-19738G>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.472-19738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,168 control chromosomes in the GnomAD database, including 2,336 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 0.17 (2336 hom., cov: 33)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINX1	NM_017884.6	c.472-19738G>A		intron_variant	Intron 6 of 6	ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.395-19738G>A		intron_variant	Intron 5 of 5		NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.472-19738G>A		intron_variant	Intron 6 of 6	1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.394+40498G>A		intron_variant	Intron 5 of 5	2		ENSP00000451145.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25822 AN: 152050 Hom.: 2334 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.170 AC: 25841 AN: 152168 Hom.: 2336 Cov.: 33 AF XY: 0.164 AC XY: 12228 AN XY: 74394

African (AFR) AF: 0.159 AC: 6598 AN: 41516

American (AMR) AF: 0.133 AC: 2028 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3472

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5186

South Asian (SAS) AF: 0.152 AC: 734 AN: 4824

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10588

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13402 AN: 67972

Other (OTH) AF: 0.186 AC: 393 AN: 2114

Alfa AF: 0.192 Hom.: 5732

Bravo AF: 0.168

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.13
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: rs9657541; hg19: chr8-10643164;