rs112062713
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001174150.2(ARL13B):c.1261A>G(p.Ser421Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001174150.2 missense
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 |
---|---|---|---|---|---|---|---|
ARL13B | NM_001174150.2 | c.1261A>G | p.Ser421Gly | missense_variant | 10/10 | ENST00000394222.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARL13B | ENST00000394222.8 | c.1261A>G | p.Ser421Gly | missense_variant | 10/10 | 1 | NM_001174150.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000335 AC: 51AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251008Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135708
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461160Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 726906
GnomAD4 genome ? AF: 0.000335 AC: 51AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74338
ClinVar
Submissions by phenotype
Joubert syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 421 of the ARL13B protein (p.Ser421Gly). This variant is present in population databases (rs112062713, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ARL13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 405194). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at