Variant 17-3636603-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000381870.8(CTNS):c.-335C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 211,556 control chromosomes in the GnomAD database, including 478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 291 hom., cov: 33)

Exomes 𝑓: 0.073 ( 187 hom. )

Consequence

CTNS
ENST00000381870.8 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.579

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-3636603-C-T is Benign according to our data. Variant chr17-3636603-C-T is described in ClinVar as [Benign]. Clinvar id is 322818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-3636603-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNS	NM_001031681.3 linkuse as main transcript	c.-335C>T		5_prime_UTR_variant	1/13
CTNS	XM_006721463.4 linkuse as main transcript	c.-330C>T		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNS	ENST00000381870.8 linkuse as main transcript	c.-335C>T		5_prime_UTR_variant	1/13	1			O60931-2
CTNS	ENST00000673965.1 linkuse as main transcript	c.-330C>T		5_prime_UTR_variant	1/12			P1	O60931-1

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9199

AN:

152228

Hom.:

287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0439

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0491

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0811

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0728

Gnomad OTH

AF:

0.0573

GnomAD4 exome

AF:

0.0726

AC:

4296

AN:

59210

Hom.:

187

Cov.:

AF XY:

0.0716

AC XY:

2200

AN XY:

30742

show subpopulations

Gnomad4 AFR exome

AF:

0.0443

Gnomad4 AMR exome

AF:

0.0566

Gnomad4 ASJ exome

AF:

0.0991

Gnomad4 EAS exome

AF:

0.000238

Gnomad4 SAS exome

AF:

0.0877

Gnomad4 FIN exome

AF:

0.0698

Gnomad4 NFE exome

AF:

0.0786

Gnomad4 OTH exome

AF:

0.0779

GnomAD4 genome

AF:

0.0605

AC:

9223

AN:

152346

Hom.:

291

Cov.:

AF XY:

0.0596

AC XY:

4442

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0440

Gnomad4 AMR

AF:

0.0491

Gnomad4 ASJ

AF:

0.0919

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0818

Gnomad4 FIN

AF:

0.0643

Gnomad4 NFE

AF:

0.0728

Gnomad4 OTH

AF:

0.0619

Alfa

AF:

0.0687

Hom.:

364

Bravo

AF:

0.0578

Asia WGS

AF:

0.0360

AC:

127

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

- -

Nephropathic cystinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

7.7

Dann

Benign

0.83

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