NM_004168.4:c.-61T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004168.4(SDHA):​c.-61T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,425,986 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000059 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

SDHA
NM_004168.4 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0520

Publications

0 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDHANM_004168.4 linkc.-61T>C upstream_gene_variant ENST00000264932.11 NP_004159.2 P31040-1A0A024QZ30
CCDC127NM_145265.3 linkc.-213A>G upstream_gene_variant ENST00000296824.4 NP_660308.1 Q96BQ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDHAENST00000264932.11 linkc.-61T>C upstream_gene_variant 1 NM_004168.4 ENSP00000264932.6 P31040-1
CCDC127ENST00000296824.4 linkc.-213A>G upstream_gene_variant 1 NM_145265.3 ENSP00000296824.2 Q96BQ5
ENSG00000286001ENST00000651543.1 linkn.-61T>C upstream_gene_variant ENSP00000499215.1 A0A494C1T6

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
151916
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000294
AC:
374
AN:
1273962
Hom.:
1
Cov.:
28
AF XY:
0.000279
AC XY:
175
AN XY:
626536
show subpopulations
African (AFR)
AF:
0.0000779
AC:
2
AN:
25674
American (AMR)
AF:
0.00
AC:
0
AN:
20124
Ashkenazi Jewish (ASJ)
AF:
0.000148
AC:
3
AN:
20226
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29766
South Asian (SAS)
AF:
0.0000158
AC:
1
AN:
63240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32522
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3614
European-Non Finnish (NFE)
AF:
0.000352
AC:
361
AN:
1026838
Other (OTH)
AF:
0.000135
AC:
7
AN:
51958
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
17
34
52
69
86
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
22
44
66
88
110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152024
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74354
show subpopulations
African (AFR)
AF:
0.0000483
AC:
2
AN:
41426
American (AMR)
AF:
0.00
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5148
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.000103
AC:
7
AN:
67950
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
8.4
DANN
Benign
0.29
PhyloP100
0.052
PromoterAI
0.012
Neutral
Mutation Taster
=300/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs943005857; hg19: chr5-218410; API