rs1052523

Positions:

• chr8-10834732-G-A
• chr8-10834732-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017884.6(PINX1):​c.63C>T​(p.Ala21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,613,460 control chromosomes in the GnomAD database, including 2,477 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 0.048 (212 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2265 hom.)
• Consequence: PINX1 NM_017884.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.52

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-6.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINX1	NM_017884.6	c.63C>T	p.Ala21=	synonymous_variant	2/7	ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.63C>T	p.Ala21=	synonymous_variant	2/6		NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.63C>T	p.Ala21=	synonymous_variant	2/7	1	NM_017884.6	ENSP00000318966	P2

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7356 AN: 152056 Hom.: 212 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0627

GnomAD3 exomes AF: 0.0495 AC: 12327 AN: 249084 Hom.: 391 AF XY: 0.0520 AC XY: 7025 AN XY: 135134

Gnomad AFR exome AF: 0.0399

Gnomad AMR exome AF: 0.0385

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0680

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0538

Gnomad OTH exome AF: 0.0685

GnomAD4 exome AF: 0.0526 AC: 76895 AN: 1461286 Hom.: 2265 Cov.: 32 AF XY: 0.0534 AC XY: 38795 AN XY: 726958

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0679

Gnomad4 FIN exome AF: 0.0374

Gnomad4 NFE exome AF: 0.0532

Gnomad4 OTH exome AF: 0.0575

GnomAD4 genome AF: 0.0483 AC: 7356 AN: 152174 Hom.: 212 Cov.: 33 AF XY: 0.0486 AC XY: 3618 AN XY: 74394

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0773

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0524

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0467 Hom.: 115

Bravo AF: 0.0494

Asia WGS AF: 0.0380 AC: 133 AN: 3478

EpiCase AF: 0.0600

EpiControl AF: 0.0616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.67

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: rs1052523; hg19: chr8-10692242;