rs550138374
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_205836.3(FBXO38):c.3439A>G(p.Met1147Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,068 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 (★★).
Frequency
Consequence
NM_205836.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBXO38 | NM_205836.3 | c.3439A>G | p.Met1147Val | missense_variant | Exon 22 of 22 | ENST00000340253.10 | NP_995308.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBXO38 | ENST00000340253.10 | c.3439A>G | p.Met1147Val | missense_variant | Exon 22 of 22 | 5 | NM_205836.3 | ENSP00000342023.6 | ||
FBXO38 | ENST00000394370.7 | c.3214A>G | p.Met1072Val | missense_variant | Exon 22 of 22 | 1 | ENSP00000377895.3 | |||
FBXO38 | ENST00000513826.1 | c.2704A>G | p.Met902Val | missense_variant | Exon 20 of 20 | 1 | ENSP00000426410.1 | |||
FBXO38 | ENST00000296701.10 | c.2704A>G | p.Met902Val | missense_variant | Exon 21 of 21 | 2 | ENSP00000296701.6 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251084Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135688
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727216
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74398
ClinVar
Submissions by phenotype
Distal hereditary motor neuropathy type 2 Uncertain:1
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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 576603). This missense change has been observed in at least one individual who was not affected with FBXO38-related conditions (Invitae). This variant has not been reported in the literature in individuals affected with FBXO38-related conditions. This variant is present in population databases (rs550138374, gnomAD 0.03%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1072 of the FBXO38 protein (p.Met1072Val). -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at