13-99606742-C-T

Variant summary

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

The NM_206808.5(CLYBL):​c.47C>T​(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,331,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CLYBL
NM_206808.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0540
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]

Genome browser will be placed here

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=0.114489436).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLYBLNM_206808.5 linkc.47C>T p.Ala16Val 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.47C>T p.Ala16Val missense_variant Exon 1 of 9 1 NM_206808.5 ENSP00000342991.4 Q8N0X4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.0000150
AC:
20
AN:
1331502
Hom.:
0
Cov.:
35
AF XY:
0.0000137
AC XY:
9
AN XY:
656920
show subpopulations
Gnomad4 AFR exome
AF:
0.0000371
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000137
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the CLYBL gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.054
T;.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.60
.;T;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;L;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.030
N;N;N
REVEL
Benign
0.044
Sift
Benign
0.28
T;T;T
Sift4G
Benign
0.36
T;T;T
Polyphen
0.0040
B;B;B
Vest4
0.33
MutPred
0.44
Loss of disorder (P = 0.0212);Loss of disorder (P = 0.0212);Loss of disorder (P = 0.0212);
MVP
0.20
ClinPred
0.51
D
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.037
gMVP
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775057322; hg19: chr13-100258996; API