NM_152384.3:c.584A>G
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 1P and 13B.
The NM_152384.3(BBS5):c.584A>G(p.Asp195Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,611,756 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D195D) has been classified as Likely benign.
Frequency
Consequence
NM_152384.3 missense
Scores
Clinical Significance
Conservation
Publications
- Bardet-Biedl syndrome 5Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- Bardet-Biedl syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BBS5 | NM_152384.3 | c.584A>G | p.Asp195Gly | missense_variant | Exon 7 of 12 | ENST00000295240.8 | NP_689597.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BBS5 | ENST00000295240.8 | c.584A>G | p.Asp195Gly | missense_variant | Exon 7 of 12 | 1 | NM_152384.3 | ENSP00000295240.3 | ||
ENSG00000251569 | ENST00000513963.1 | c.584A>G | p.Asp195Gly | missense_variant | Exon 7 of 16 | 2 | ENSP00000424363.1 |
Frequencies
GnomAD3 genomes AF: 0.00183 AC: 279AN: 152234Hom.: 4 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00634 AC: 1593AN: 251228 AF XY: 0.00440 show subpopulations
GnomAD4 exome AF: 0.00132 AC: 1933AN: 1459404Hom.: 46 Cov.: 29 AF XY: 0.00104 AC XY: 754AN XY: 726154 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00183 AC: 279AN: 152352Hom.: 4 Cov.: 32 AF XY: 0.00179 AC XY: 133AN XY: 74506 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:3
- -
- -
- -
not provided Uncertain:1
The D195G variant in the BBS5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D195G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Aspartic Acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D195G as a variant of uncertain significance. -
Bardet-Biedl syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at