chr11-1753665-C-G

Variant names:

• chr11-1753665-C-G
• rs138940129
• NM_001909.5:c.1077G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001909.5(CTSD):​c.1077G>C​(p.Ser359Ser) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S359S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTSD NM_001909.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.73
• Publications: 0 publications found

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]

CTSD Gene-Disease associations (from GenCC):

• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 10

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

ENSG00000250644 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 11-1753665-C-G is Benign according to our data. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1753665-C-G is described in CliVar as Likely_benign. Clinvar id is 2707847.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.73 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSD	NM_001909.5	c.1077G>C	p.Ser359Ser	synonymous_variant	Exon 9 of 9	ENST00000236671.7	NP_001900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSD	ENST00000236671.7	c.1077G>C	p.Ser359Ser	synonymous_variant	Exon 9 of 9	1	NM_001909.5	ENSP00000236671.2
ENSG00000250644	ENST00000636615.1	c.1071+138G>C		intron_variant	Intron 8 of 9	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neuronal ceroid lipofuscinosis Benign:1

Jun 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.12
DANN	Benign	0.78
PhyloP100		-4.7
PromoterAI		-0.0043	Neutral

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

Other links and lift over

dbSNP: rs138940129; hg19: chr11-1774895;