13-99606726-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_206808.5(CLYBL):​c.31C>T​(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,490,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 𝑓 0.00082 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CLYBL
NM_206808.5 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.818

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008576959).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLYBLNM_206808.5 linkc.31C>T p.Arg11Cys 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>T p.Arg11Cys missense_variant Exon 1 of 9 1 NM_206808.5 ENSP00000342991.4 Q8N0X4-1

Frequencies

GnomAD3 genomes
AF:
0.000818
AC:
124
AN:
151596
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00282
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000394
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000109
AC:
11
AN:
100508
AF XY:
0.000106
show subpopulations
Gnomad AFR exome
AF:
0.00368
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000499
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000209
AC:
280
AN:
1338644
Hom.:
0
Cov.:
35
AF XY:
0.000215
AC XY:
142
AN XY:
660684
show subpopulations
African (AFR)
AF:
0.00380
AC:
103
AN:
27134
American (AMR)
AF:
0.0000993
AC:
3
AN:
30218
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23548
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29686
South Asian (SAS)
AF:
0.0000814
AC:
6
AN:
73742
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36108
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4156
European-Non Finnish (NFE)
AF:
0.000150
AC:
159
AN:
1058422
Other (OTH)
AF:
0.000162
AC:
9
AN:
55630
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
18
36
55
73
91
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000817
AC:
124
AN:
151706
Hom.:
0
Cov.:
31
AF XY:
0.000876
AC XY:
65
AN XY:
74174
show subpopulations
African (AFR)
AF:
0.00281
AC:
116
AN:
41226
American (AMR)
AF:
0.000394
AC:
6
AN:
15232
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5146
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10570
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
67938
Other (OTH)
AF:
0.00
AC:
0
AN:
2098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
5
10
14
19
24
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000490
Hom.:
0
Bravo
AF:
0.000997
ESP6500AA
AF:
0.00218
AC:
8
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000143
AC:
14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.081
T;.;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.68
.;T;T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.0086
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;L;L
PhyloP100
0.82
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.010
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.97
D;D;D
Vest4
0.30
MVP
0.43
ClinPred
0.10
T
GERP RS
3.5
PromoterAI
0.078
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.20
gMVP
0.49
Mutation Taster
=87/13
polymorphism

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

Other links and lift over

dbSNP: rs184570178; hg19: chr13-100258980; API