11-1754038-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_001909.5(CTSD):c.928G>A(p.Glu310Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000602 in 1,610,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001909.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSD | NM_001909.5 | c.928G>A | p.Glu310Lys | missense_variant | 7/9 | ENST00000236671.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSD | ENST00000236671.7 | c.928G>A | p.Glu310Lys | missense_variant | 7/9 | 1 | NM_001909.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 243898Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132816
GnomAD4 exome AF: 0.0000652 AC: 95AN: 1458088Hom.: 0 Cov.: 38 AF XY: 0.0000538 AC XY: 39AN XY: 725350
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74308
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 10 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 13, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2017 | p.Glu310Lys (GAG>AAG): c.928 G>A in exon 7 of the CTSD gene (NM_001909.4). A variant of unknown significance has been identified in the CTSD gene. The E310K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The E310K variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The E310K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s). - |
Neuronal ceroid lipofuscinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 310 of the CTSD protein (p.Glu310Lys). This variant is present in population databases (rs373699222, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CTSD-related conditions. ClinVar contains an entry for this variant (Variation ID: 205341). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at