rs560932680

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000651543.1(ENSG00000286001):​n.-1C>G 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 0.00000753 in 1,460,982 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 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

ENSG00000286001
ENST00000651543.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.522

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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDHANM_004168.4 linkc.-1C>G 5_prime_UTR_variant Exon 1 of 15 ENST00000264932.11 NP_004159.2 P31040-1A0A024QZ30
CCDC127NM_145265.3 linkc.-273G>C upstream_gene_variant ENST00000296824.4 NP_660308.1 Q96BQ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000286001ENST00000651543.1 linkn.-1C>G non_coding_transcript_exon_variant Exon 1 of 24 ENSP00000499215.1 A0A494C1T6
SDHAENST00000264932.11 linkc.-1C>G 5_prime_UTR_variant Exon 1 of 15 1 NM_004168.4 ENSP00000264932.6 P31040-1
ENSG00000286001ENST00000651543.1 linkn.-1C>G 5_prime_UTR_variant Exon 1 of 24 ENSP00000499215.1 A0A494C1T6
CCDC127ENST00000296824.4 linkc.-273G>C upstream_gene_variant 1 NM_145265.3 ENSP00000296824.2 Q96BQ5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152204
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000174
AC:
2
AN:
114728
AF XY:
0.0000301
show subpopulations
Gnomad AFR exome
AF:
0.000161
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000458
AC:
6
AN:
1308670
Hom.:
0
Cov.:
31
AF XY:
0.00000619
AC XY:
4
AN XY:
646094
show subpopulations
African (AFR)
AF:
0.0000372
AC:
1
AN:
26880
American (AMR)
AF:
0.00
AC:
0
AN:
25048
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20460
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31054
South Asian (SAS)
AF:
0.0000301
AC:
2
AN:
66346
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33976
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3700
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1047642
Other (OTH)
AF:
0.0000560
AC:
3
AN:
53564
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152312
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74476
show subpopulations
African (AFR)
AF:
0.0000962
AC:
4
AN:
41568
American (AMR)
AF:
0.0000653
AC:
1
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68022
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1
Jan 31, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.-1C>G variant is located in the 5' untranslated region (5&rsquo; UTR) of the SDHA gene. This variant results from a C to G substitution 1 bases upstream from the first translated codon. This nucleotide position is well conserved in available vertebrate species. Based on the available evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
9.7
DANN
Benign
0.76
PhyloP100
0.52
PromoterAI
-0.41
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=298/2
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: rs560932680; hg19: chr5-218470; API