rs878855040
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_017882.3(CLN6):c.61_62insCGG(p.Leu20_Gly21insAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000818 in 1,467,142 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G21G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000084 ( 0 hom. )
Consequence
CLN6
NM_017882.3 conservative_inframe_insertion
NM_017882.3 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.360
Publications
0 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: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, Genomics England PanelApp, G2P
- ceroid lipofuscinosis, neuronal, 6B (Kufs type)Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp
- neuronal ceroid lipofuscinosisInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_017882.3. Strenght limited to Supporting due to length of the change: 1aa.
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CLN6 | NM_017882.3 | MANE Select | c.61_62insCGG | p.Leu20_Gly21insAla | conservative_inframe_insertion | Exon 1 of 7 | NP_060352.1 | Q9NWW5-1 | |
| CLN6 | NM_001411068.1 | c.180-10874_180-10873insCGG | intron | N/A | NP_001397997.1 | Q9NWW5-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CLN6 | ENST00000249806.11 | TSL:1 MANE Select | c.61_62insCGG | p.Leu20_Gly21insAla | conservative_inframe_insertion | Exon 1 of 7 | ENSP00000249806.5 | Q9NWW5-1 | |
| CLN6 | ENST00000637667.1 | TSL:1 | c.61_62insCGG | p.Leu20_Gly21insAla | conservative_inframe_insertion | Exon 1 of 6 | ENSP00000489843.1 | A0A1B0GTU6 | |
| CLN6 | ENST00000566347.5 | TSL:1 | c.61_62insCGG | p.Leu20_Gly21insAla | conservative_inframe_insertion | Exon 1 of 6 | ENSP00000457783.1 | H3BUT1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151992
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000836 AC: 11AN: 1315150Hom.: 0 Cov.: 31 AF XY: 0.0000108 AC XY: 7AN XY: 648416 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1315150
Hom.:
Cov.:
31
AF XY:
AC XY:
7
AN XY:
648416
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26468
American (AMR)
AF:
AC:
0
AN:
27026
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22886
East Asian (EAS)
AF:
AC:
0
AN:
28242
South Asian (SAS)
AF:
AC:
0
AN:
73124
European-Finnish (FIN)
AF:
AC:
0
AN:
32636
Middle Eastern (MID)
AF:
AC:
0
AN:
3910
European-Non Finnish (NFE)
AF:
AC:
11
AN:
1046610
Other (OTH)
AF:
AC:
0
AN:
54248
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
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2
2
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4
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0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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4
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Age
GnomAD4 genome 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74256 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151992
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
74256
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41432
American (AMR)
AF:
AC:
0
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10526
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67970
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Neuronal ceroid lipofuscinosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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