GeneBe

rs1553409736

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001378454.1(ALMS1):​c.8524C>G​(p.His2842Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H2842Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ALMS1
NM_001378454.1 missense

Scores

14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.379

Publications

0 publications found
Variant links:
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 syndrome
    Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04935366).

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ALMS1
NM_001378454.1
MANE Select
c.8524C>Gp.His2842Asp
missense
Exon 10 of 23NP_001365383.1Q8TCU4-1
ALMS1
NM_015120.4
c.8524C>Gp.His2842Asp
missense
Exon 10 of 23NP_055935.4Q8TCU4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ALMS1
ENST00000613296.6
TSL:1 MANE Select
c.8524C>Gp.His2842Asp
missense
Exon 10 of 23ENSP00000482968.1Q8TCU4-1
ALMS1
ENST00000484298.5
TSL:1
c.8398C>Gp.His2800Asp
missense
Exon 9 of 22ENSP00000478155.1A0A087WTU9
ALMS1
ENST00000423048.5
TSL:1
n.3030+325C>G
intron
N/AENSP00000399833.1H7C1D9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
33

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Alstrom syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
11
DANN
Benign
0.94
DEOGEN2
Benign
0.025
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-0.94
T
PhyloP100
0.38
PrimateAI
Benign
0.31
T
Sift4G
Benign
0.96
T
Vest4
0.21
MVP
0.099
ClinPred
0.051
T
GERP RS
0.023
Varity_R
0.050
gMVP
0.080
Mutation Taster
=88/12
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1553409736; hg19: chr2-73717610; API