17-3662938-C-T

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

2

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]
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]
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]

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
CTNSNM_004937.3 linkc.*2569C>T 3_prime_UTR_variant Exon 12 of 12 ENST00000046640.9 NP_004928.2 O60931-1A0A0S2Z3K3
TAX1BP3NM_014604.4 linkc.*810G>A 3_prime_UTR_variant Exon 4 of 4 ENST00000225525.4 NP_055419.1 O14907

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTNSENST00000046640.9 linkc.*2569C>T 3_prime_UTR_variant Exon 12 of 12 1 NM_004937.3 ENSP00000046640.4 O60931-1
TAX1BP3ENST00000225525 linkc.*810G>A 3_prime_UTR_variant Exon 4 of 4 1 NM_014604.4 ENSP00000225525.3 O14907
TAX1BP3ENST00000611779 linkc.*810G>A 3_prime_UTR_variant Exon 3 of 3 2 ENSP00000484776.1 A0A087X282
P2RX5-TAX1BP3ENST00000550383.1 linkn.*4542G>A downstream_gene_variant 2 ENSP00000455681.1

Frequencies

GnomAD3 genomes
AF:
0.347
AC:
52714
AN:
151998
Hom.:
9805
Cov.:
33
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:
3
AN:
10
Hom.:
1
Cov.:
0
AF XY:
0.167
AC XY:
1
AN XY:
6
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.:
33
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

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. -

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.

Other links and lift over

dbSNP: rs7093; hg19: chr17-3566232; API