NM_004937.3:c.779C>A

Variant names:

• chr17-3658102-C-A
• rs161400
• NM_004937.3:c.779C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. T260S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 36)
• Consequence: CTNS NM_004937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 42 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.779C>A	p.Thr260Asn	missense	Exon 10 of 12	NP_004928.2	O60931-1
	CTNS	NM_001031681.3		c.779C>A	p.Thr260Asn	missense	Exon 10 of 13	NP_001026851.2	O60931-2
	CTNS	NM_001374492.1		c.779C>A	p.Thr260Asn	missense	Exon 10 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.779C>A	p.Thr260Asn	missense	Exon 10 of 12	ENSP00000046640.4	O60931-1
	CTNS	ENST00000381870.8	TSL:1	c.779C>A	p.Thr260Asn	missense	Exon 10 of 13	ENSP00000371294.3	O60931-2
	CTNS	ENST00000673965.1		c.779C>A	p.Thr260Asn	missense	Exon 10 of 12	ENSP00000500995.1	O60931-1

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.013	D
Polyphen		0.18	B
Vest4		0.37
MutPred		0.29		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

Other links and lift over

dbSNP: rs161400; hg19: chr17-3561396;