17-3656529-G-C

Variant names:

• chr17-3656529-G-C
• NM_004937.3:c.504G>C
• CTNS p.Thr168Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004937.3(CTNS):​c.504G>C​(p.Thr168Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T168T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CTNS NM_004937.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823
• 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-AS1 (HGNC:56090): (CTNS antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.823 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004937.3. 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_004937.3	MANE Select	c.504G>C	p.Thr168Thr	synonymous	Exon 8 of 12	NP_004928.2	O60931-1
	CTNS	NM_001031681.3		c.504G>C	p.Thr168Thr	synonymous	Exon 8 of 13	NP_001026851.2	O60931-2
	CTNS	NM_001374492.1		c.504G>C	p.Thr168Thr	synonymous	Exon 8 of 13	NP_001361421.1	O60931-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNS	ENST00000046640.9	TSL:1 MANE Select	c.504G>C	p.Thr168Thr	synonymous	Exon 8 of 12	ENSP00000046640.4	O60931-1
	CTNS	ENST00000381870.8	TSL:1	c.504G>C	p.Thr168Thr	synonymous	Exon 8 of 13	ENSP00000371294.3	O60931-2
	CTNS	ENST00000673965.1		c.504G>C	p.Thr168Thr	synonymous	Exon 8 of 12	ENSP00000500995.1	O60931-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-3559823;