NM_004168.4:c.-61T>A

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

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]

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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
SDHANM_004168.4 linkc.-61T>A upstream_gene_variant ENST00000264932.11 NP_004159.2 P31040-1A0A024QZ30
CCDC127NM_145265.3 linkc.-213A>T 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>A upstream_gene_variant 1 NM_004168.4 ENSP00000264932.6 P31040-1
CCDC127ENST00000296824.4 linkc.-213A>T upstream_gene_variant 1 NM_145265.3 ENSP00000296824.2 Q96BQ5
ENSG00000286001ENST00000651543.1 linkn.-61T>A upstream_gene_variant ENSP00000499215.1 A0A494C1T6

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1273984
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
626550
African (AFR)
AF:
0.00
AC:
0
AN:
25678
American (AMR)
AF:
0.00
AC:
0
AN:
20124
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20228
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29766
South Asian (SAS)
AF:
0.00
AC:
0
AN:
63242
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:
0.00
AC:
0
AN:
1026848
Other (OTH)
AF:
0.00
AC:
0
AN:
51962
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
7.8
DANN
Benign
0.45
PhyloP100
0.052
PromoterAI
-0.017
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

hg19: chr5-218410; API