NM_015447.4:c.4193C>G
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015447.4(CAMSAP1):c.4193C>G(p.Ser1398*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CAMSAP1
NM_015447.4 stop_gained
NM_015447.4 stop_gained
Scores
5
1
Clinical Significance
Conservation
PhyloP100: 9.57
Publications
1 publications found
Genes affected
CAMSAP1 (HGNC:19946): (calmodulin regulated spectrin associated protein 1) Enables microtubule minus-end binding activity and spectrin binding activity. Involved in several processes, including neuron projection development; regulation of cell morphogenesis; and regulation of microtubule polymerization. Located in microtubule. Colocalizes with microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]
CAMSAP1 Gene-Disease associations (from GenCC):
- cortical dysplasia, complex, with other brain malformations 12Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
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 9-135818055-G-C is Pathogenic according to our data. Variant chr9-135818055-G-C is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 1706471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_015447.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CAMSAP1 | MANE Select | c.4193C>G | p.Ser1398* | stop_gained | Exon 14 of 17 | NP_056262.3 | Q5T5Y3-1 | ||
| CAMSAP1 | c.4226C>G | p.Ser1409* | stop_gained | Exon 15 of 18 | NP_001424208.1 | ||||
| CAMSAP1 | c.3761C>G | p.Ser1254* | stop_gained | Exon 13 of 16 | NP_001424209.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CAMSAP1 | TSL:5 MANE Select | c.4193C>G | p.Ser1398* | stop_gained | Exon 14 of 17 | ENSP00000374183.4 | Q5T5Y3-1 | ||
| CAMSAP1 | TSL:1 | c.3359C>G | p.Ser1120* | stop_gained | Exon 12 of 15 | ENSP00000312463.6 | Q5T5Y3-2 | ||
| CAMSAP1 | TSL:5 | c.4226C>G | p.Ser1409* | stop_gained | Exon 15 of 18 | ENSP00000386420.3 | Q5T5Y3-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461458Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727030 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1461458
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727030
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53204
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111840
Other (OTH)
AF:
AC:
0
AN:
60366
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0404278), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
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
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
CAMSAP1-related neuronal migration disorder (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
PhyloP100
Vest4
GERP RS
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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