rs17711777

Variant names:

• chr8-10765730-T-C
• rs17711777
• NM_017884.6:c.658A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 21 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]

ENSG00000248896 (HGNC:58246):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017884.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	NM_017884.6	MANE Select	c.658A>G	p.Thr220Ala	missense	Exon 7 of 7	NP_060354.4
	PINX1	NM_001284356.2		c.*56A>G		3_prime_UTR	Exon 6 of 6	NP_001271285.1
	SOX7-AS1	NR_146188.1		n.341-2670T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	ENST00000314787.8	TSL:1 MANE Select	c.658A>G	p.Thr220Ala	missense	Exon 7 of 7	ENSP00000318966.3
	PINX1	ENST00000519088.5	TSL:1	c.*56A>G		3_prime_UTR	Exon 6 of 6	ENSP00000428853.1
	PINX1	ENST00000554914.1	TSL:2	c.395-39064A>G		intron	N/A	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

GnomAD2 exomes AF: 0.0725 AC: 18064 AN: 249206 AF XY: 0.0663

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 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

African (AFR) AF: 0.0102 AC: 342 AN: 33480

American (AMR) AF: 0.198 AC: 8838 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 865 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.0262 AC: 2263 AN: 86258

European-Finnish (FIN) AF: 0.0744 AC: 3971 AN: 53384

Middle Eastern (MID) AF: 0.0212 AC: 122 AN: 5768

European-Non Finnish (NFE) AF: 0.0707 AC: 78578 AN: 1111836

Other (OTH) AF: 0.0573 AC: 3461 AN: 60372

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

African (AFR) AF: 0.0136 AC: 564 AN: 41572

American (AMR) AF: 0.113 AC: 1736 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5172

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4828

European-Finnish (FIN) AF: 0.0790 AC: 838 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4613 AN: 68016

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0622 Hom.: 1560

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 v4.9

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
PhyloP100		0.82
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
Mutation Taster		=97/3	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: rs17711777; hg19: chr8-10623240; COSMIC: COSV59111692; COSMIC: COSV59111692;