rs145106503
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_ModerateBP6BS1
The NM_003849.4(SUCLG1):c.721G>A(p.Glu241Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,613,772 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
SUCLG1
NM_003849.4 missense
NM_003849.4 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
SUCLG1 (HGNC:11449): (succinate-CoA ligase GDP/ADP-forming subunit alpha) This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11008805).
BP6
?
Variant 2-84431612-C-T is Benign according to our data. Variant chr2-84431612-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 579004.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000388 (59/152078) while in subpopulation AFR AF= 0.00135 (56/41408). AF 95% confidence interval is 0.00107. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUCLG1 | NM_003849.4 | c.721G>A | p.Glu241Lys | missense_variant | 7/9 | ENST00000393868.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUCLG1 | ENST00000393868.7 | c.721G>A | p.Glu241Lys | missense_variant | 7/9 | 1 | NM_003849.4 | P1 | |
SUCLG1 | ENST00000487809.1 | n.468G>A | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
SUCLG1 | ENST00000491123.5 | n.567G>A | non_coding_transcript_exon_variant | 2/4 | 3 | ||||
SUCLG1 | ENST00000651342.1 | c.*161G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/10 |
Frequencies
GnomAD3 genomes ? AF: 0.000388 AC: 59AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251188Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135774
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727150
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GnomAD4 genome ? AF: 0.000388 AC: 59AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.000310 AC XY: 23AN XY: 74288
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 9 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at