rs746405582
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001080517.3(SETD5):c.245C>T(p.Pro82Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. P82P) has been classified as Benign.
Frequency
Consequence
NM_001080517.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD5 | NM_001080517.3 | c.245C>T | p.Pro82Leu | missense_variant | 5/23 | ENST00000402198.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD5 | ENST00000402198.7 | c.245C>T | p.Pro82Leu | missense_variant | 5/23 | 5 | NM_001080517.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249140Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135162
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461698Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727130
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 24, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 436692). This sequence change replaces proline with leucine at codon 82 of the SETD5 protein (p.Pro82Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs746405582, ExAC 0.006%). This missense change has been observed in individual(s) with features of SETD5-related neurodevelopmental syndrome (Invitae). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at