rs184570178

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_206808.5(CLYBL):​c.31C>A​(p.Arg11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,338,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

CLYBL
NM_206808.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.818
Variant links:
Genes affected
CLYBL (HGNC:18355): (citramalyl-CoA lyase) Enables (S)-citramalyl-CoA lyase activity; magnesium ion binding activity; and malate synthase activity. Involved in protein homotrimerization and regulation of cobalamin metabolic process. Predicted to be located in mitochondrion. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16259414).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLYBLNM_206808.5 linkc.31C>A p.Arg11Ser missense_variant Exon 1 of 9 ENST00000339105.9 NP_996531.1 Q8N0X4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLYBLENST00000339105.9 linkc.31C>A p.Arg11Ser missense_variant Exon 1 of 9 1 NM_206808.5 ENSP00000342991.4 Q8N0X4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.47e-7
AC:
1
AN:
1338646
Hom.:
0
Cov.:
35
AF XY:
0.00000151
AC XY:
1
AN XY:
660684
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000136
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.023
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.073
T;.;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.51
.;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;L;L
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.52
N;N;N
REVEL
Benign
0.11
Sift
Benign
0.074
T;T;T
Sift4G
Uncertain
0.023
D;D;D
Polyphen
0.31
B;P;B
Vest4
0.41
MutPred
0.38
Loss of methylation at R11 (P = 0.0013);Loss of methylation at R11 (P = 0.0013);Loss of methylation at R11 (P = 0.0013);
MVP
0.38
ClinPred
0.82
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.17
gMVP
0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-100258980; API