rs560868487

Positions:

• chr17-3660347-C-A
• chr17-3660347-C-G
• chr17-3660347-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004937.3(CTNS):​c.1082C>A​(p.Pro361Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CTNS NM_004937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13160771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNS	NM_004937.3	c.1082C>A	p.Pro361Gln	missense_variant	12/12	ENST00000046640.9	NP_004928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNS	ENST00000046640.9	c.1082C>A	p.Pro361Gln	missense_variant	12/12	1	NM_004937.3	ENSP00000046640	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251412 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461836 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	0.0047
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.62	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.95	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.10	T;D
Sift4G	Benign	0.18	T;D
Polyphen		0.20	B;P
Vest4		0.097
MutPred		0.23		Loss of glycosylation at P361 (P = 0.0246);Loss of glycosylation at P361 (P = 0.0246);
MVP		0.94
MPC		0.51
ClinPred		0.62	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs560868487; hg19: chr17-3563641;