chr16-28487536-CG-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001042432.2(CLN3):c.379delC(p.Arg127GlyfsTer54) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R127R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CLN3
NM_001042432.2 frameshift
NM_001042432.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.15
Publications
1 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: Ambry Genetics, Genomics England PanelApp, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 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 16-28487536-CG-C is Pathogenic according to our data. Variant chr16-28487536-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 56267.Status of the report is criteria_provided_single_submitter, 1 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 | MANE Select | c.379delC | p.Arg127GlyfsTer54 | frameshift | Exon 7 of 16 | NP_001035897.1 | Q13286-1 | ||
| CLN3 | c.379delC | p.Arg127GlyfsTer54 | frameshift | Exon 6 of 15 | NP_000077.1 | Q13286-1 | |||
| CLN3 | c.307delC | p.Arg103GlyfsTer54 | frameshift | Exon 6 of 15 | NP_001273033.1 | Q13286-7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CLN3 | TSL:1 MANE Select | c.379delC | p.Arg127GlyfsTer54 | frameshift | Exon 7 of 16 | ENSP00000490105.1 | Q13286-1 | ||
| CLN3 | TSL:1 | c.379delC | p.Arg127GlyfsTer54 | frameshift | Exon 6 of 15 | ENSP00000353073.9 | Q13286-1 | ||
| CLN3 | TSL:1 | c.379delC | p.Arg127GlyfsTer54 | frameshift | Exon 6 of 14 | ENSP00000456117.1 | Q13286-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250934 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250934
AF XY:
Gnomad AFR exome
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Gnomad FIN exome
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Gnomad NFE exome
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461624Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727150 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461624
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
727150
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
1
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53372
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111832
Other (OTH)
AF:
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Neuronal ceroid lipofuscinosis (1)
1
-
-
Neuronal ceroid lipofuscinosis 3 (1)
1
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-
Retinitis pigmentosa (1)
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
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