rs104893679
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001278293.3(ARL6):āc.506G>Cā(p.Gly169Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G169C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001278293.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARL6 | NM_001278293.3 | c.506G>C | p.Gly169Ala | missense_variant | 7/8 | ENST00000463745.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARL6 | ENST00000463745.6 | c.506G>C | p.Gly169Ala | missense_variant | 7/8 | 2 | NM_001278293.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461464Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727058
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 3;C3150808:Retinitis pigmentosa 55 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 169 of the ARL6 protein (p.Gly169Ala). This variant is present in population databases (rs104893679, gnomAD 0.0009%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 15314642). It has also been observed to segregate with disease in related individuals. This variant is also known as 859G>C G169A. ClinVar contains an entry for this variant (Variation ID: 2041). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects ARL6 function (PMID: 19236846). For these reasons, this variant has been classified as Pathogenic. - |
Bardet-Biedl syndrome 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2004 | - - |
Bardet-Biedl syndrome 1, modifier of Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Sep 01, 2004 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at