chr4-102869103-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001008388.5(CISD2):c.19G>A(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,459,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A7A) has been classified as Likely benign.
Frequency
Consequence
NM_001008388.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CISD2 | NM_001008388.5 | c.19G>A | p.Ala7Thr | missense_variant | 1/3 | ENST00000273986.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CISD2 | ENST00000273986.10 | c.19G>A | p.Ala7Thr | missense_variant | 1/3 | 1 | NM_001008388.5 | P1 | |
CISD2 | ENST00000574446.1 | c.19G>A | p.Ala7Thr | missense_variant, NMD_transcript_variant | 1/4 | 5 | |||
CISD2 | ENST00000646632.1 | c.19G>A | p.Ala7Thr | missense_variant, NMD_transcript_variant | 1/4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245806Hom.: 0 AF XY: 0.00000750 AC XY: 1AN XY: 133282
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459806Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6AN XY: 725966
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CISD2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 7 of the CISD2 protein (p.Ala7Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at