chr11-61430157-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_017841.4(SDHAF2):c.11C>G(p.Ser4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign 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. S4A) has been classified as Uncertain significance.
Frequency
Consequence
NM_017841.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHAF2 | NM_017841.4 | c.11C>G | p.Ser4Cys | missense_variant | 1/4 | ENST00000301761.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHAF2 | ENST00000301761.7 | c.11C>G | p.Ser4Cys | missense_variant | 1/4 | 1 | NM_017841.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250728Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135652
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727214
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74392
ClinVar
Submissions by phenotype
Hereditary pheochromocytoma-paraganglioma Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Apr 27, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 647376). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. This variant is present in population databases (rs778449586, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 4 of the SDHAF2 protein (p.Ser4Cys). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. - |
Paragangliomas 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 30, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 2023 | The p.S4C variant (also known as c.11C>G), located in coding exon 1 of the SDHAF2 gene, results from a C to G substitution at nucleotide position 11. The serine at codon 4 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at