15-68214373-C-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017882.3(CLN6):āc.214G>Cā(p.Glu72Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00127 in 1,613,736 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_017882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN6 | NM_017882.3 | c.214G>C | p.Glu72Gln | missense_variant | Exon 3 of 7 | ENST00000249806.11 | NP_060352.1 | |
CLN6 | NM_001411068.1 | c.310G>C | p.Glu104Gln | missense_variant | Exon 3 of 7 | NP_001397997.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00162 AC: 247AN: 152220Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00262 AC: 659AN: 251428Hom.: 8 AF XY: 0.00331 AC XY: 450AN XY: 135902
GnomAD4 exome AF: 0.00123 AC: 1804AN: 1461398Hom.: 29 Cov.: 30 AF XY: 0.00171 AC XY: 1243AN XY: 727036
GnomAD4 genome AF: 0.00162 AC: 247AN: 152338Hom.: 3 Cov.: 33 AF XY: 0.00191 AC XY: 142AN XY: 74492
ClinVar
Submissions by phenotype
not specified Benign:5
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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. -
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not provided Benign:3
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CLN6: BS1, BS2 -
Neuronal ceroid lipofuscinosis Benign:2
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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
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Ceroid lipofuscinosis, neuronal, 6B (Kufs type) Benign:1
The heterozygous p.Glu72Gln variant in GLN6 has been identified in at least 1 Indian individual with late infantile neuronal ceroid lipofuscinosis (PMID: 12815591), but has also been identified in >1% of South Asian chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive late infantile neuronal ceroid lipofuscinosis. -
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at