8-10785654-C-T

Variant summary

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

The NM_017884.6(PINX1):c.472-19738G>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

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=-0.54).
• 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/exons	MANE	UniProt
PINX1	NM_017884.6	c.472-19738G>A		intron_variant		ENST00000314787.8
PINX1	NM_001284356.2	c.395-19738G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINX1	ENST00000314787.8	c.472-19738G>A		intron_variant		1	NM_017884.6	P2
PINX1	ENST00000519088.5	c.395-19738G>A		intron_variant		1		A2
PINX1	ENST00000524114.6	c.502-19738G>A		intron_variant		3		A2
PINX1	ENST00000523559.1	c.*191+1970G>A		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.186

Alfa AF: 0.192 Hom.: 4032

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

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: rs9657541; hg19: chr8-10643164;