chr11-1761364-G-C

Variant names:

• chr11-1761364-G-C
• NM_001909.5:c.173C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001909.5(CTSD):​c.173C>G​(p.Ala58Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. A58V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTSD NM_001909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027784228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSD	NM_001909.5	c.173C>G	p.Ala58Gly	missense_variant	Exon 2 of 9	ENST00000236671.7	NP_001900.1
PRADX	NR_182291.1	n.893G>C		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.173C>G	p.Ala58Gly	missense_variant	Exon 2 of 9	1	NM_001909.5	ENSP00000236671.2
ENSG00000250644	ENST00000636615.1	c.173C>G	p.Ala58Gly	missense_variant	Exon 2 of 10	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.2
DANN	Benign	0.54
DEOGEN2	Benign	0.25	.;.;T;T;.;T;.;T;.;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.49	T;T;T;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.028	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	.;.;N;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.87	.;.;N;.;.;.;.;.;N;N;.
REVEL	Benign	0.074
Sift	Benign	1.0	.;.;T;.;.;.;.;.;T;T;.
Sift4G	Benign	0.74	.;.;T;.;.;.;.;.;T;.;.
Polyphen		0.0	.;.;B;.;.;.;.;.;.;.;.
Vest4		0.074
MutPred		0.23		Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);Gain of disorder (P = 0.0724);.;.;.;
MVP		0.19
MPC		0.50
ClinPred		0.048	T
GERP RS		-1.7
Varity_R		0.025
gMVP		0.50

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: chr11-1782594;