rs1240316419

Variant names:

• chr11-1761436-C-G
• NM_001909.5:c.101G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-1761436-C-G
• chr11-1761436-C-T

Variant summary

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

The NM_001909.5(CTSD):​c.101G>C​(p.Arg34Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTSD NM_001909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

Genes affected

CTSD (HGNC:2529): (cathepsin D) This gene encodes a member of the A1 family of peptidases. The encoded preproprotein is proteolytically processed to generate multiple protein products. These products include the cathepsin D light and heavy chains, which heterodimerize to form the mature enzyme. This enzyme exhibits pepsin-like activity and plays a role in protein turnover and in the proteolytic activation of hormones and growth factors. Mutations in this gene play a causal role in neuronal ceroid lipofuscinosis-10 and may be involved in the pathogenesis of several other diseases, including breast cancer and possibly Alzheimer's disease. [provided by RefSeq, Nov 2015]

ENSG00000250644 (HGNC:):

PRADX (HGNC:40168): (PRC2 and DDX5 associated lncRNA)

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 rank	MANE	Protein	UniProt
CTSD	NM_001909.5	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 9	ENST00000236671.7	NP_001900.1
PRADX	NR_182291.1	n.965C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSD	ENST00000236671.7	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 9	1	NM_001909.5	ENSP00000236671.2
ENSG00000250644	ENST00000636615.1	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 10	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461566 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727088

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	.;.;D;T;.;T;.;T;.
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.7	.;.;M;.;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.3	.;.;D;.;.;.;.;.;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	.;.;D;.;.;.;.;.;D
Sift4G	Uncertain	0.029	.;.;D;.;.;.;.;.;D
Polyphen		1.0	.;.;D;.;.;.;.;.;.
Vest4		0.42
MutPred		0.57		Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);.;
MVP		0.65
MPC		1.7
ClinPred		0.99	D
GERP RS		-0.22
Varity_R		0.87
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-1782666;