17-3662938-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004937.3(CTNS):c.*2569C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,126 control chromosomes in the GnomAD database, including 9,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9807 hom., cov: 33)

Exomes 𝑓: 0.30 ( 1 hom. )

Consequence

CTNS
NM_004937.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

CTNS (HGNC:2518): (cystinosin, lysosomal cystine transporter) This gene encodes a seven-transmembrane domain protein that functions to transport cystine out of lysosomes. Its activity is driven by the H+ electrochemical gradient of the lysosomal membrane. Mutations in this gene cause cystinosis, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

CTNS links:

TAX1BP3 (HGNC:30684): (Tax1 binding protein 3) This gene encodes a small, highly conserved protein with a single PDZ domain. PDZ (PSD-95/Discs large/ZO-1 homologous) domains promote protein-protein interactions that affect cell signaling, adhesion, protein scaffolding, and receptor and ion transporter functions. The encoded protein interacts with a large number of target proteins that play roles in signaling pathways; for example, it interacts with Rho A and glutaminase L and also acts as a negative regulator of the Wnt/beta-catenin signaling pathway. This protein was first identified as binding to the T-cell leukaemia virus (HTLV1) Tax oncoprotein. Overexpression of this gene has been implicated in altered cancer cell adhesion, migration and metastasis. The encoded protein also modulates the localization and density of inwardly rectifying potassium channel 2.3 (Kir2.3). To date, this protein has been shown to play a role in cell proliferation, development, stress response, and polarization. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

TAX1BP3 links:

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

P2RX5-TAX1BP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-3662938-C-T is Benign according to our data. Variant chr17-3662938-C-T is described in ClinVar as [Benign]. Clinvar id is 322920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNS	NM_004937.3 link	c.*2569C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000046640.9	NP_004928.2	O60931-1A0A0S2Z3K3
TAX1BP3	NM_014604.4 link	c.*810G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000225525.4	NP_055419.1	O14907

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTNS	ENST00000046640.9 link	c.*2569C>T	3_prime_UTR_variant	Exon 12 of 12	1	NM_004937.3	ENSP00000046640.4	O60931-1
TAX1BP3	ENST00000225525 link	c.*810G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_014604.4	ENSP00000225525.3	O14907
TAX1BP3	ENST00000611779 link	c.*810G>A	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000484776.1	A0A087X282
P2RX5-TAX1BP3	ENST00000550383.1 link	n.*4542G>A	downstream_gene_variant		2		ENSP00000455681.1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52714

AN:

151998

Hom.:

9805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.300

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.347

AC:

52738

AN:

152116

Hom.:

9807

Cov.:

AF XY:

0.345

AC XY:

25674

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.381

Hom.:

4317

Bravo

AF:

0.348

Asia WGS

AF:

0.435

AC:

1513

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ocular cystinosis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nephropathic cystinosis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.58

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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