chr17-3656425-CTGTCCCTCCACCCCTGCCAGTCTTCACCCCCTGCCCTGTCT-C

Position:

• chr17-3656425-CTGTCCCTCCACCCCTGCCAGTCTTCACCCCCTGCCCTGTCT-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_004937.3(CTNS):​c.462-47_462-7del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000519 in 904,784 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., cov: 7)
  • Exomes 𝑓: 0.000054 (1 hom.)
• Consequence: CTNS NM_004937.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.907

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-AS1 (HGNC:56090): (CTNS antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-3656425-CTGTCCCTCCACCCCTGCCAGTCTTCACCCCCTGCCCTGTCT-C is Benign according to our data. Variant chr17-3656425-CTGTCCCTCCACCCCTGCCAGTCTTCACCCCCTGCCCTGTCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 2925136.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNS	NM_004937.3	c.462-47_462-7del		intron_variant		ENST00000046640.9	NP_004928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNS	ENST00000046640.9	c.462-47_462-7del		intron_variant		1	NM_004937.3	ENSP00000046640	P1
CTNS-AS1	ENST00000575741.1	n.532+390_532+430del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 1 AN: 56568 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.0000918

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000542 AC: 46 AN: 848194 Hom.: 1 AF XY: 0.0000730 AC XY: 32 AN XY: 438550

Gnomad4 AFR exome AF: 0.000295

Gnomad4 AMR exome AF: 0.0000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.000308

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000513

Gnomad4 OTH exome AF: 0.0000777

GnomAD4 genome AF: 0.0000177 AC: 1 AN: 56590 Hom.: 0 Cov.: 7 AF XY: 0.0000383 AC XY: 1 AN XY: 26120

Gnomad4 AFR AF: 0.0000913

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Juvenile nephropathic cystinosis;C0950123:Inborn genetic diseases;C2931013:Ocular cystinosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 03, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2076147522; hg19: chr17-3559719;