Variant 8-10765540-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017884.6(PINX1):c.848C>T(p.Pro283Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,480 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

PINX1
NM_017884.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.595

Variant links:

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]

PINX1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08703303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PINX1	NM_017884.6 linkuse as main transcript	c.848C>T	p.Pro283Leu	missense_variant	7/7	ENST00000314787.8	NP_060354.4
LOC102723313	NR_146188.1 linkuse as main transcript	n.341-2860G>A		intron_variant, non_coding_transcript_variant
PINX1	NM_001284356.2 linkuse as main transcript	c.*246C>T		3_prime_UTR_variant	6/6		NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8 linkuse as main transcript	c.848C>T	p.Pro283Leu	missense_variant	7/7	1	NM_017884.6	ENSP00000318966	P2	Q96BK5-1
	ENST00000657150.1 linkuse as main transcript	n.174-2860G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

248896

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135062

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461410

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.848C>T (p.P283L) alteration is located in exon 7 (coding exon 7) of the PINX1 gene. This alteration results from a C to T substitution at nucleotide position 848, causing the proline (P) at amino acid position 283 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.085

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.48

M_CAP

Benign

0.0037

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-1.7

REVEL

Benign

0.048

Sift

Uncertain

0.0030

Sift4G

Benign

0.086

Polyphen

0.071

Vest4

0.16

MVP

0.51

MPC

0.0015

ClinPred

0.088

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.055

gMVP

0.016

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over