chr16-28486464-CCT-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001042432.2(CLN3):c.558_559delAG(p.Gly187AspfsTer48) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S186S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CLN3
NM_001042432.2 frameshift
NM_001042432.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.52
Publications
4 publications found
Genes affected
CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
CLN3 Gene-Disease associations (from GenCC):
- inherited retinal dystrophyInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- neuronal ceroid lipofuscinosisInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- neuronal ceroid lipofuscinosis 3Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Myriad Women’s Health, Ambry Genetics, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-28486464-CCT-C is Pathogenic according to our data. Variant chr16-28486464-CCT-C is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 56280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001042432.2. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CLN3 | NM_001042432.2 | MANE Select | c.558_559delAG | p.Gly187AspfsTer48 | frameshift | Exon 9 of 16 | NP_001035897.1 | Q13286-1 | |
| CLN3 | NM_000086.2 | c.558_559delAG | p.Gly187AspfsTer48 | frameshift | Exon 8 of 15 | NP_000077.1 | Q13286-1 | ||
| CLN3 | NM_001286104.2 | c.486_487delAG | p.Gly163AspfsTer48 | frameshift | Exon 8 of 15 | NP_001273033.1 | Q13286-7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CLN3 | ENST00000636147.2 | TSL:1 MANE Select | c.558_559delAG | p.Gly187AspfsTer48 | frameshift | Exon 9 of 16 | ENSP00000490105.1 | Q13286-1 | |
| CLN3 | ENST00000359984.12 | TSL:1 | c.558_559delAG | p.Gly187AspfsTer48 | frameshift | Exon 8 of 15 | ENSP00000353073.9 | Q13286-1 | |
| CLN3 | ENST00000565316.6 | TSL:1 | c.558_559delAG | p.Gly187AspfsTer48 | frameshift | Exon 8 of 14 | ENSP00000456117.1 | Q13286-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000404 AC: 1AN: 247310 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
247310
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461050Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726796 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461050
Hom.:
AF XY:
AC XY:
0
AN XY:
726796
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44580
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26092
East Asian (EAS)
AF:
AC:
0
AN:
39684
South Asian (SAS)
AF:
AC:
0
AN:
86114
European-Finnish (FIN)
AF:
AC:
0
AN:
53230
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111756
Other (OTH)
AF:
AC:
0
AN:
60354
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Neuronal ceroid lipofuscinosis (2)
2
-
-
Neuronal ceroid lipofuscinosis 3 (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.