rs752534676
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001034850.3(RETREG1):c.443G>C(p.Arg148Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R148G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001034850.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RETREG1 | NM_001034850.3 | c.443G>C | p.Arg148Thr | missense_variant | 3/9 | ENST00000306320.10 | |
RETREG1 | XM_011514053.4 | c.443G>C | p.Arg148Thr | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RETREG1 | ENST00000306320.10 | c.443G>C | p.Arg148Thr | missense_variant | 3/9 | 1 | NM_001034850.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249004Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135080
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461698Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727112
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2023 | The c.443G>C (p.R148T) alteration is located in exon 3 (coding exon 3) of the FAM134B gene. This alteration results from a G to C substitution at nucleotide position 443, causing the arginine (R) at amino acid position 148 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2022 | This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 148 of the RETREG1 protein (p.Arg148Thr). This variant is present in population databases (rs752534676, gnomAD 0.004%). 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: 573479). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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