NM_001378454.1:c.9113delC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001378454.1(ALMS1):c.9113delC(p.Pro3038LeufsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 frameshift
NM_001378454.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.37
Publications
0 publications found
Genes affected
ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]
ALMS1 Gene-Disease associations (from GenCC):
- Alstrom syndromeInheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, 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 2-73491070-TC-T is Pathogenic according to our data. Variant chr2-73491070-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 438278.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001378454.1. 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 |
|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | NM_001378454.1 | MANE Select | c.9113delC | p.Pro3038LeufsTer12 | frameshift | Exon 10 of 23 | NP_001365383.1 | Q8TCU4-1 | |
| ALMS1 | NM_015120.4 | c.9113delC | p.Pro3038LeufsTer12 | frameshift | Exon 10 of 23 | NP_055935.4 | Q8TCU4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | ENST00000613296.6 | TSL:1 MANE Select | c.9113delC | p.Pro3038LeufsTer12 | frameshift | Exon 10 of 23 | ENSP00000482968.1 | Q8TCU4-1 | |
| ALMS1 | ENST00000484298.5 | TSL:1 | c.8987delC | p.Pro2996LeufsTer12 | frameshift | Exon 9 of 22 | ENSP00000478155.1 | A0A087WTU9 | |
| ALMS1 | ENST00000423048.5 | TSL:1 | n.3030+914delC | intron | N/A | ENSP00000399833.1 | H7C1D9 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152226
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461868Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727226 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461868
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727226
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112000
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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0
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1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152226
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74368
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41464
American (AMR)
AF:
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68038
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
Age Distribution
Genome Het
Variant carriers
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10
<30
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Age
Alfa
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Hom.:
Bravo
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ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
2
-
-
Alstrom syndrome (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
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