chr5-16475066-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001034850.3(RETREG1):c.1169C>T(p.Thr390Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,748 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T390T) has been classified as Likely benign.
Frequency
Consequence
NM_001034850.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RETREG1 | NM_001034850.3 | c.1169C>T | p.Thr390Met | missense_variant | 9/9 | ENST00000306320.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RETREG1 | ENST00000306320.10 | c.1169C>T | p.Thr390Met | missense_variant | 9/9 | 1 | NM_001034850.3 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152114Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248808Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134958
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461634Hom.: 0 Cov.: 35 AF XY: 0.0000289 AC XY: 21AN XY: 727118
GnomAD4 genome AF: 0.000112 AC: 17AN: 152114Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74298
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2019 | The p.T390M variant (also known as c.1169C>T), located in coding exon 9 of the FAM134B gene, results from a C to T substitution at nucleotide position 1169. The threonine at codon 390 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Neuropathy, hereditary sensory and autonomic, type 2B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 390 of the RETREG1 protein (p.Thr390Met). This variant is present in population databases (rs374082497, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with RETREG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 579199). 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 methionine 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