13-76992095-C-T
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_006493.4(CLN5):c.-4C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,611,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006493.4 5_prime_UTR
Scores
Clinical Significance
Conservation
Publications
- neuronal ceroid lipofuscinosisInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- neuronal ceroid lipofuscinosis 5Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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CLN5 | NM_006493.4 | c.-4C>T | 5_prime_UTR_variant | Exon 1 of 4 | ENST00000377453.9 | NP_006484.2 | ||
CLN5 | NM_001366624.2 | c.-4C>T | 5_prime_UTR_variant | Exon 1 of 5 | NP_001353553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN5 | ENST00000377453.9 | c.-4C>T | 5_prime_UTR_variant | Exon 1 of 4 | 1 | NM_006493.4 | ENSP00000366673.5 | |||
ENSG00000283208 | ENST00000638147.2 | c.-4C>T | 5_prime_UTR_variant | Exon 1 of 5 | 5 | ENSP00000490953.2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152156Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000302 AC: 71AN: 234874 AF XY: 0.000317 show subpopulations
GnomAD4 exome AF: 0.000149 AC: 217AN: 1459560Hom.: 0 Cov.: 35 AF XY: 0.000167 AC XY: 121AN XY: 726118 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000118 AC: 18AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74332 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 5 Uncertain:1Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive Uncertain:1
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not specified Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
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Neuronal ceroid lipofuscinosis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at