rs1052523

Variant names:

• chr8-10834732-G-A
• rs1052523
• NM_017884.6:c.63C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017884.6(PINX1):​c.63C>T​(p.Ala21Ala) 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
• Publications: 10 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 -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 rank	MANE	Protein	UniProt
PINX1	NM_017884.6	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 7	ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 6		NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 7	1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 6	2		ENSP00000451145.1

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

GnomAD2 exomes AF: 0.0495 AC: 12327 AN: 249084 AF XY: 0.0520

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 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

African (AFR) AF: 0.0405 AC: 1354 AN: 33472

American (AMR) AF: 0.0409 AC: 1827 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2657 AN: 26126

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0679 AC: 5858 AN: 86230

European-Finnish (FIN) AF: 0.0374 AC: 1994 AN: 53352

Middle Eastern (MID) AF: 0.0977 AC: 563 AN: 5764

European-Non Finnish (NFE) AF: 0.0532 AC: 59164 AN: 1111586

Other (OTH) AF: 0.0575 AC: 3473 AN: 60354

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

African (AFR) AF: 0.0407 AC: 1691 AN: 41520

American (AMR) AF: 0.0504 AC: 770 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0773 AC: 373 AN: 4826

European-Finnish (FIN) AF: 0.0341 AC: 360 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0524 AC: 3562 AN: 68002

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0487 Hom.: 168

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
PhyloP100		-6.5
Mutation Taster		=99/1	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: rs1052523; hg19: chr8-10692242;