15-68211858-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_017882.3(CLN6):c.303C>T(p.Ile101Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,202 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 Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
CLN6
NM_017882.3 synonymous
NM_017882.3 synonymous
Scores
3
Clinical Significance
Conservation
PhyloP100: -0.488
Publications
1 publications found
Genes affected
CLN6 (HGNC:2077): (CLN6 transmembrane ER protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function. [provided by RefSeq, Oct 2008]
CLN6 Gene-Disease associations (from GenCC):
- ceroid lipofuscinosis, neuronal, 6AInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
- ceroid lipofuscinosis, neuronal, 6B (Kufs type)Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
- neuronal ceroid lipofuscinosisInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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=-0.63).
BP6
Variant 15-68211858-G-A is Benign according to our data. Variant chr15-68211858-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 527777.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.488 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_017882.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CLN6 | NM_017882.3 | MANE Select | c.303C>T | p.Ile101Ile | synonymous | Exon 4 of 7 | NP_060352.1 | ||
| CLN6 | NM_001411068.1 | c.399C>T | p.Ile133Ile | synonymous | Exon 4 of 7 | NP_001397997.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CLN6 | ENST00000249806.11 | TSL:1 MANE Select | c.303C>T | p.Ile101Ile | synonymous | Exon 4 of 7 | ENSP00000249806.5 | ||
| CLN6 | ENST00000637667.1 | TSL:1 | c.204C>T | p.Ile68Ile | synonymous | Exon 3 of 6 | ENSP00000489843.1 | ||
| CLN6 | ENST00000638076.1 | TSL:1 | n.303C>T | non_coding_transcript_exon | Exon 4 of 7 | ENSP00000490373.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00 AC: 0AN: 250124 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
250124
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461202Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 726862 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1461202
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
726862
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
1
AN:
86242
European-Finnish (FIN)
AF:
AC:
0
AN:
52964
Middle Eastern (MID)
AF:
AC:
0
AN:
5662
European-Non Finnish (NFE)
AF:
AC:
10
AN:
1111946
Other (OTH)
AF:
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.452
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neuronal ceroid lipofuscinosis Benign:1
Jan 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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