rs373260107

Variant names:

• chr17-3636585-G-A
• rs373260107
• ENST00000381870.8:c.-353G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-3636585-G-A
• chr17-3636585-G-C
• chr17-3636585-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001031681.3(CTNS):​c.-353G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 231,548 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00082 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: CTNS NM_001031681.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0790
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• cystinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
• nephropathic cystinosis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics
• juvenile nephropathic cystinosis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• ocular cystinosis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• nephropathic infantile cystinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-3636585-G-A is Benign according to our data. Variant chr17-3636585-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 322817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000821 (125/152316) while in subpopulation SAS AF = 0.0236 (114/4828). AF 95% confidence interval is 0.0201. There are 4 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031681.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNS	NM_001031681.3		c.-353G>A		5_prime_UTR	Exon 1 of 13	NP_001026851.2	O60931-2
	CTNS	NM_004937.3	MANE Select	c.-476G>A		upstream_gene	N/A	NP_004928.2	O60931-1
	CTNS	NM_001374492.1		c.-476G>A		upstream_gene	N/A	NP_001361421.1	O60931-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNS	ENST00000381870.8	TSL:1	c.-353G>A		5_prime_UTR	Exon 1 of 13	ENSP00000371294.3	O60931-2
	CTNS	ENST00000673965.1		c.-348G>A		5_prime_UTR	Exon 1 of 12	ENSP00000500995.1	O60931-1
	CTNS	ENST00000901058.1		c.-353G>A		5_prime_UTR	Exon 1 of 12	ENSP00000571117.1

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152198 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00143 AC: 113 AN: 79232 Hom.: 0 Cov.: 0 AF XY: 0.00216 AC XY: 88 AN XY: 40724

African (AFR) AF: 0.00 AC: 0 AN: 2502

American (AMR) AF: 0.00 AC: 0 AN: 2002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3080

East Asian (EAS) AF: 0.000846 AC: 5 AN: 5908

South Asian (SAS) AF: 0.0207 AC: 107 AN: 5164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 416

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49818

Other (OTH) AF: 0.000190 AC: 1 AN: 5266

GnomAD4 genome AF: 0.000821 AC: 125 AN: 152316 Hom.: 4 Cov.: 33 AF XY: 0.00128 AC XY: 95 AN XY: 74482

African (AFR) AF: 0.0000481 AC: 2 AN: 41592

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000166

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Nephropathic cystinosis (1)
-	-	1	Ocular cystinosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.3
DANN	Benign	0.84
PhyloP100		0.079
PromoterAI		0.11	Neutral

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: rs373260107; hg19: chr17-3539879;