rs368354870
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001378454.1(ALMS1):c.331C>A(p.Pro111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,754 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P111A) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 missense
NM_001378454.1 missense
Scores
1
6
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.10
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 Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | ENST00000613296.6 | c.331C>A | p.Pro111Thr | missense_variant | Exon 2 of 23 | 1 | NM_001378454.1 | ENSP00000482968.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151992
Hom.:
Cov.:
31
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: 6.85e-7 AC: 1AN: 1460762Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726718 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1460762
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726718
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:
33438
American (AMR)
AF:
AC:
0
AN:
44674
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26090
East Asian (EAS)
AF:
AC:
0
AN:
39632
South Asian (SAS)
AF:
AC:
1
AN:
86208
European-Finnish (FIN)
AF:
AC:
0
AN:
53310
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111326
Other (OTH)
AF:
AC:
0
AN:
60322
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74228 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151992
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74228
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41356
American (AMR)
AF:
AC:
0
AN:
15236
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10572
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68022
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PhyloP100
PrimateAI
Benign
T
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0744);Gain of MoRF binding (P = 0.0744);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
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.