5-225976-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2
The NM_004168.4(SDHA):c.550G>A(p.Gly184Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,614,116 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G184A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004168.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHA | NM_004168.4 | c.550G>A | p.Gly184Arg | missense_variant | 5/15 | ENST00000264932.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHA | ENST00000264932.11 | c.550G>A | p.Gly184Arg | missense_variant | 5/15 | 1 | NM_004168.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000815 AC: 124AN: 152180Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00155 AC: 391AN: 251488Hom.: 1 AF XY: 0.00146 AC XY: 199AN XY: 135920
GnomAD4 exome AF: 0.000679 AC: 993AN: 1461818Hom.: 14 Cov.: 33 AF XY: 0.000646 AC XY: 470AN XY: 727202
GnomAD4 genome AF: 0.000808 AC: 123AN: 152298Hom.: 2 Cov.: 33 AF XY: 0.000873 AC XY: 65AN XY: 74472
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 11, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 12, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 13, 2019 | - - |
Mitochondrial complex II deficiency, nuclear type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Paragangliomas 5;C5700310:Mitochondrial complex II deficiency, nuclear type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Leigh syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 05, 2017 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Paragangliomas 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Hereditary pheochromocytoma-paraganglioma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at