5-218349-A-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_004168.4(SDHA):c.-7A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,455,416 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004168.4 5_prime_UTR
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 rank | MANE | Protein | UniProt |
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SDHA | NM_004168.4 | c.-7A>C | 5_prime_UTR_variant | Exon 1 of 15 | ENST00000264932.11 | NP_004159.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHA | ENST00000264932 | c.-7A>C | 5_prime_UTR_variant | Exon 1 of 15 | 1 | NM_004168.4 | ENSP00000264932.6 | |||
ENSG00000286001 | ENST00000651543.1 | n.-7A>C | non_coding_transcript_exon_variant | Exon 1 of 24 | ENSP00000499215.1 | |||||
ENSG00000286001 | ENST00000651543.1 | n.-7A>C | 5_prime_UTR_variant | Exon 1 of 24 | ENSP00000499215.1 |
Frequencies
GnomAD3 genomes AF: 0.000789 AC: 120AN: 152162Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000666 AC: 72AN: 108066Hom.: 0 AF XY: 0.000800 AC XY: 50AN XY: 62516
GnomAD4 exome AF: 0.00103 AC: 1341AN: 1303146Hom.: 1 Cov.: 31 AF XY: 0.00105 AC XY: 673AN XY: 642938
GnomAD4 genome AF: 0.000782 AC: 119AN: 152270Hom.: 0 Cov.: 34 AF XY: 0.000672 AC XY: 50AN XY: 74454
ClinVar
Submissions by phenotype
not provided Benign:5
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SDHA: BS1 -
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not specified Uncertain:1Benign:2
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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. -
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
The c.-7A>C alteration is located in the 5' untranslated region (5'UTR) of the SDHA gene. This alteration consists of a A to C substitution nucleotides upstream from the first translated codon. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
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Paragangliomas 5 Uncertain:1Benign:1
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This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
Mitochondrial complex II deficiency, nuclear type 1 Uncertain:1
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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Leigh syndrome Uncertain:1
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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Paragangliomas 5;C5700310:Mitochondrial complex II deficiency, nuclear type 1 Benign:1
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Hereditary pheochromocytoma-paraganglioma Benign:1
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at