12-108562654-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_213595.4(ISCU):āc.32G>Cā(p.Arg11Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000239 in 1,460,934 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11W) has been classified as Uncertain significance.
Frequency
Consequence
NM_213595.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ISCU | NM_213595.4 | c.32G>C | p.Arg11Pro | missense_variant | 1/5 | ENST00000311893.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ISCU | ENST00000311893.14 | c.32G>C | p.Arg11Pro | missense_variant | 1/5 | 1 | NM_213595.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152198Hom.: 0 Cov.: 36
GnomAD3 exomes AF: 0.0000531 AC: 4AN: 75306Hom.: 1 AF XY: 0.0000924 AC XY: 4AN XY: 43272
GnomAD4 exome AF: 0.000254 AC: 332AN: 1308624Hom.: 2 Cov.: 35 AF XY: 0.000249 AC XY: 160AN XY: 643456
GnomAD4 genome AF: 0.000112 AC: 17AN: 152310Hom.: 0 Cov.: 36 AF XY: 0.0000940 AC XY: 7AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 11 of the ISCU protein (p.Arg11Pro). This variant is present in population databases (rs550874413, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ISCU-related conditions. ClinVar contains an entry for this variant (Variation ID: 1406161). 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: "Not Available"; 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2023 | The c.32G>C (p.R11P) alteration is located in exon 1 (coding exon 1) of the ISCU gene. This alteration results from a G to C substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at