rs161400

Positions:

• chr17-3658102-C-A
• chr17-3658102-C-G
• chr17-3658102-C-T

Variant summary

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

The NM_004937.3(CTNS):​c.779C>A​(p.Thr260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T260I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 36)
• Consequence: CTNS NM_004937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNS	NM_004937.3	c.779C>A	p.Thr260Asn	missense_variant	10/12	ENST00000046640.9	NP_004928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNS	ENST00000046640.9	c.779C>A	p.Thr260Asn	missense_variant	10/12	1	NM_004937.3	ENSP00000046640	P1
CTNS-AS1	ENST00000575741.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	0.038
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.069	P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.18	B;D
Vest4		0.37
MutPred		0.29		Loss of glycosylation at T260 (P = 0.0116);Loss of glycosylation at T260 (P = 0.0116);
MVP		0.90
MPC		0.47
ClinPred		0.88	D
GERP RS		2.9
Varity_R		0.12
gMVP		0.63

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

Other links and lift over

dbSNP: rs161400; hg19: chr17-3561396;