3-67400808-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003848.4(SUCLG2):c.1106G>T(p.Cys369Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,612,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
SUCLG2
NM_003848.4 missense
NM_003848.4 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
SUCLG2 (HGNC:11450): (succinate-CoA ligase GDP-forming subunit beta) This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.928
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SUCLG2 | ENST00000307227.10 | c.1106G>T | p.Cys369Phe | missense_variant | 10/11 | 1 | NM_003848.4 | ENSP00000307432.5 | ||
SUCLG2 | ENST00000493112.5 | c.1106G>T | p.Cys369Phe | missense_variant | 10/11 | 1 | ENSP00000419325.1 | |||
SUCLG2 | ENST00000460567.5 | c.377G>T | p.Cys126Phe | missense_variant | 4/5 | 1 | ENSP00000417260.1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000442 AC: 11AN: 248696Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134982
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460580Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726640
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GnomAD4 genome AF: 0.000177 AC: 27AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74330
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The c.1106G>T (p.C369F) alteration is located in exon 10 (coding exon 10) of the SUCLG2 gene. This alteration results from a G to T substitution at nucleotide position 1106, causing the cysteine (C) at amino acid position 369 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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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