rs878855001

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000613296.6(ALMS1):​c.7670C>T​(p.Ser2557Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S2557S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ALMS1
ENST00000613296.6 missense

Scores

3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALMS1NM_001378454.1 linkuse as main transcriptc.7670C>T p.Ser2557Phe missense_variant 9/23 ENST00000613296.6 NP_001365383.1
ALMS1NM_015120.4 linkuse as main transcriptc.7673C>T p.Ser2558Phe missense_variant 9/23 NP_055935.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALMS1ENST00000613296.6 linkuse as main transcriptc.7670C>T p.Ser2557Phe missense_variant 9/231 NM_001378454.1 ENSP00000482968 P3Q8TCU4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Alstrom syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 11, 2023This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2558 of the ALMS1 protein (p.Ser2558Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 241011). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.51
D;D;D
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
0.65
D;N;N
PrimateAI
Benign
0.36
T
Sift4G
Uncertain
0.012
D;D;D
Vest4
0.55
MVP
0.33
ClinPred
0.89
D
GERP RS
1.2
Varity_R
0.041
gMVP
0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs878855001; hg19: chr2-73682418; API