rs1553403345
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001378454.1(ALMS1):c.1965G>A(p.Val655=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V655V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378454.1 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.1965G>A | p.Val655= | synonymous_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.1968G>A | p.Val656= | synonymous_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.1965G>A | p.Val655= | synonymous_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248596Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134814
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461756Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0AN XY: 727190
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2020 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with ALMS1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 656 of the ALMS1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ALMS1 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at