NM_004168.4:c.-61T>A
Variant names: 
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004168.4(SDHA):c.-61T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
 Genomes: not found (cov: 34) 
 Exomes 𝑓:  0.0   (  0   hom.  ) 
 Failed GnomAD Quality Control 
Consequence
 SDHA
NM_004168.4 upstream_gene
NM_004168.4 upstream_gene
Scores
 2
Clinical Significance
 Not reported in ClinVar 
Conservation
 PhyloP100:  0.0520  
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] 
 CCDC127  (HGNC:30520):  (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022] 
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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=-0.77). 
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt | 
|---|---|---|---|---|---|---|---|---|
| SDHA | NM_004168.4 | c.-61T>A | upstream_gene_variant | ENST00000264932.11 | NP_004159.2 | |||
| CCDC127 | NM_145265.3 | c.-213A>T | upstream_gene_variant | ENST00000296824.4 | NP_660308.1 | 
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt | 
|---|---|---|---|---|---|---|---|---|---|---|
| SDHA | ENST00000264932.11 | c.-61T>A | upstream_gene_variant | 1 | NM_004168.4 | ENSP00000264932.6 | ||||
| CCDC127 | ENST00000296824.4 | c.-213A>T | upstream_gene_variant | 1 | NM_145265.3 | ENSP00000296824.2 | ||||
| ENSG00000286001 | ENST00000651543.1 | n.-61T>A | upstream_gene_variant | ENSP00000499215.1 | 
Frequencies
GnomAD3 genomes  
GnomAD3 genomes 
Cov.: 
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF:  0.00  AC: 0AN: 1273984Hom.:  0  Cov.: 28 AF XY:  0.00  AC XY: 0AN XY: 626550 
GnomAD4 exome 
Data not reliable, filtered out with message: AC0
 AF: 
AC: 
0
AN: 
1273984
Hom.: 
Cov.: 
28
 AF XY: 
AC XY: 
0
AN XY: 
626550
African (AFR) 
 AF: 
AC: 
0
AN: 
25678
American (AMR) 
 AF: 
AC: 
0
AN: 
20124
Ashkenazi Jewish (ASJ) 
 AF: 
AC: 
0
AN: 
20228
East Asian (EAS) 
 AF: 
AC: 
0
AN: 
29766
South Asian (SAS) 
 AF: 
AC: 
0
AN: 
63242
European-Finnish (FIN) 
 AF: 
AC: 
0
AN: 
32522
Middle Eastern (MID) 
 AF: 
AC: 
0
AN: 
3614
European-Non Finnish (NFE) 
 AF: 
AC: 
0
AN: 
1026848
Other (OTH) 
 AF: 
AC: 
0
AN: 
51962
GnomAD4 genome  
GnomAD4 genome 
Cov.: 
34
ClinVar
Not reported inComputational scores
Source: 
Name
Calibrated prediction
Score
Prediction
 BayesDel_noAF 
 Benign 
 DANN 
 Benign 
 PhyloP100 
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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