rs147565118

Variant names:

• chr17-3656505-C-A
• rs147565118
• NM_004937.3:c.480C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-3656505-C-A
• chr17-3656505-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1 PP3

The NM_004937.3(CTNS):​c.480C>A​(p.Phe160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTNS NM_004937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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 3 ACMG points.

• PM1: In a domain PQ-loop 1 (size 66) in uniprot entity CTNS_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_004937.3
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNS	NM_004937.3	c.480C>A	p.Phe160Leu	missense_variant	Exon 8 of 12	ENST00000046640.9	NP_004928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNS	ENST00000046640.9	c.480C>A	p.Phe160Leu	missense_variant	Exon 8 of 12	1	NM_004937.3	ENSP00000046640.4

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248340 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460614 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726520

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Pathogenic	0.96	D;.;.;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.93	D;D;.;D;D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	1.2	L;L;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.7	D;D;.;.;.
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;D;.;.;.
Sift4G	Pathogenic	0.0	D;D;.;D;D
Polyphen		0.61	P;D;.;.;.
Vest4		0.93
MutPred		0.62		Loss of catalytic residue at F160 (P = 0.014);Loss of catalytic residue at F160 (P = 0.014);.;.;Loss of catalytic residue at F160 (P = 0.014);
MVP		0.83
MPC		0.73
ClinPred		0.99	D
GERP RS		-8.1
Varity_R		0.88
gMVP		0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs147565118; hg19: chr17-3559799;