chr5-134606988-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_016103.4(SAR1B):c.559G>A(p.Gly187Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. G187E) has been classified as Uncertain significance.
Frequency
Consequence
NM_016103.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SAR1B | NM_016103.4 | c.559G>A | p.Gly187Arg | missense_variant | 7/7 | ENST00000402673.7 | |
SAR1B | NM_001033503.3 | c.559G>A | p.Gly187Arg | missense_variant | 8/8 | ||
SAR1B | XM_047417257.1 | c.559G>A | p.Gly187Arg | missense_variant | 7/7 | ||
SAR1B | XM_047417258.1 | c.355G>A | p.Gly119Arg | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SAR1B | ENST00000402673.7 | c.559G>A | p.Gly187Arg | missense_variant | 7/7 | 1 | NM_016103.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251446Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135892
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461786Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727212
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 187 of the SAR1B protein (p.Gly187Arg). This variant is present in population databases (rs774325300, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SAR1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1462385). 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: "Tolerated"; 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