12-108562632-G-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_213595.4(ISCU):āc.10G>Cā(p.Ala4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,473,674 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.
Frequency
Consequence
NM_213595.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ISCU | NM_213595.4 | c.10G>C | p.Ala4Pro | missense_variant | 1/5 | ENST00000311893.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ISCU | ENST00000311893.14 | c.10G>C | p.Ala4Pro | missense_variant | 1/5 | 1 | NM_213595.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00365 AC: 556AN: 152242Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.00197 AC: 189AN: 95794Hom.: 1 AF XY: 0.00200 AC XY: 111AN XY: 55494
GnomAD4 exome AF: 0.00547 AC: 7227AN: 1321316Hom.: 42 Cov.: 27 AF XY: 0.00533 AC XY: 3468AN XY: 650944
GnomAD4 genome AF: 0.00365 AC: 556AN: 152358Hom.: 0 Cov.: 35 AF XY: 0.00384 AC XY: 286AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | ISCU: BS2 - |
Hereditary myopathy with lactic acidosis due to ISCU deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 09, 2021 | - - |
ISCU-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 20, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at