rs17711777

Positions:

• chr8-10765730-T-C

Variant summary

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

The NM_017884.6(PINX1):​c.658A>G​(p.Thr220Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,613,944 control chromosomes in the GnomAD database, including 4,478 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.053 (346 hom., cov: 33)
  • Exomes 𝑓: 0.067 (4132 hom.)
• Consequence: PINX1 NM_017884.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015332103).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINX1	NM_017884.6	c.658A>G	p.Thr220Ala	missense_variant	7/7	ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.*56A>G		3_prime_UTR_variant	6/6		NP_001271285.1
LOC102723313	NR_146188.1	n.341-2670T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.658A>G	p.Thr220Ala	missense_variant	7/7	1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.395-39064A>G		intron_variant		2		ENSP00000451145.1

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8066 AN: 152170 Hom.: 339 Cov.: 33

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0425

GnomAD3 exomes AF: 0.0725 AC: 18064 AN: 249206 Hom.: 1202 AF XY: 0.0663 AC XY: 8959 AN XY: 135212

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.0341

Gnomad EAS exome AF: 0.000223

Gnomad SAS exome AF: 0.0251

Gnomad FIN exome AF: 0.0745

Gnomad NFE exome AF: 0.0656

Gnomad OTH exome AF: 0.0692

GnomAD4 exome AF: 0.0674 AC: 98448 AN: 1461656 Hom.: 4132 Cov.: 34 AF XY: 0.0656 AC XY: 47686 AN XY: 727114

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.0331

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0262

Gnomad4 FIN exome AF: 0.0744

Gnomad4 NFE exome AF: 0.0707

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0531 AC: 8081 AN: 152288 Hom.: 346 Cov.: 33 AF XY: 0.0534 AC XY: 3977 AN XY: 74464

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0790

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0617 Hom.: 764

Bravo AF: 0.0575

TwinsUK AF: 0.0609 AC: 226

ALSPAC AF: 0.0672 AC: 259

ESP6500AA AF: 0.0179 AC: 69

ESP6500EA AF: 0.0679 AC: 561

ExAC AF: 0.0653 AC: 7885

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.0644

EpiControl AF: 0.0615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.83
DANN	Benign	0.55
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.40	N
PROVEAN	Benign	0.51	N
REVEL	Benign	0.048
Sift	Benign	0.76	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.0014
ClinPred		0.0021	T
GERP RS		0.91
Varity_R		0.034
gMVP		0.036

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: rs17711777; hg19: chr8-10623240; COSMIC: COSV59111692; COSMIC: COSV59111692;