rs200020595

Variant summary

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

The NM_206808.5(CLYBL):​c.50C>G​(p.Ala17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A17S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 7.5e-7 ( 0 hom. )

Consequence

CLYBL
NM_206808.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390
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=0.17753947).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLYBLNM_206808.5 linkc.50C>G p.Ala17Gly 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.50C>G p.Ala17Gly missense_variant Exon 1 of 9 1 NM_206808.5 ENSP00000342991.4 Q8N0X4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.51e-7
AC:
1
AN:
1331088
Hom.:
0
Cov.:
35
AF XY:
0.00000152
AC XY:
1
AN XY:
656642
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000181
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
17
DANN
Benign
0.91
DEOGEN2
Benign
0.057
T;.;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.43
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.51
.;T;T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;L
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
0.010
N;N;N
REVEL
Benign
0.034
Sift
Benign
0.41
T;T;T
Sift4G
Benign
0.44
T;T;T
Polyphen
0.49
P;P;P
Vest4
0.35
MutPred
0.37
Gain of catalytic residue at A17 (P = 0.004);Gain of catalytic residue at A17 (P = 0.004);Gain of catalytic residue at A17 (P = 0.004);
MVP
0.17
ClinPred
0.40
T
GERP RS
1.6
Varity_R
0.040
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr13-100258999; API