chr5-218352-A-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000651543.1(ENSG00000286001):n.-4A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,530 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 7.7e-7 ( 0 hom. )
Consequence
ENSG00000286001
ENST00000651543.1 non_coding_transcript_exon
ENST00000651543.1 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.05
Publications
0 publications found
Genes affected
SDHA (HGNC:10680): (succinate dehydrogenase complex flavoprotein subunit A) This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SDHA | NM_004168.4 | c.-4A>C | 5_prime_UTR_variant | Exon 1 of 15 | ENST00000264932.11 | NP_004159.2 | ||
| CCDC127 | NM_145265.3 | c.-270T>G | upstream_gene_variant | ENST00000296824.4 | NP_660308.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ENSG00000286001 | ENST00000651543.1 | n.-4A>C | non_coding_transcript_exon_variant | Exon 1 of 24 | ENSP00000499215.1 | |||||
| SDHA | ENST00000264932.11 | c.-4A>C | 5_prime_UTR_variant | Exon 1 of 15 | 1 | NM_004168.4 | ENSP00000264932.6 | |||
| ENSG00000286001 | ENST00000651543.1 | n.-4A>C | 5_prime_UTR_variant | Exon 1 of 24 | ENSP00000499215.1 | |||||
| CCDC127 | ENST00000296824.4 | c.-270T>G | upstream_gene_variant | 1 | NM_145265.3 | ENSP00000296824.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152120
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 7.65e-7 AC: 1AN: 1306410Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 644660 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1306410
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
644660
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26808
American (AMR)
AF:
AC:
0
AN:
24688
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
20380
East Asian (EAS)
AF:
AC:
0
AN:
30978
South Asian (SAS)
AF:
AC:
0
AN:
66116
European-Finnish (FIN)
AF:
AC:
0
AN:
33824
Middle Eastern (MID)
AF:
AC:
0
AN:
3700
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1046446
Other (OTH)
AF:
AC:
0
AN:
53470
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74310 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152120
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
74310
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41432
American (AMR)
AF:
AC:
1
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67998
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Mar 06, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.-4A>C variant is located in the 5' untranslated region (5’ UTR) of the SDHA gene. This variant results from an A to C substitution 4 bases upstream from the first translated codon. This nucleotide position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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