13-99606745-C-G

Variant names:

• chr13-99606745-C-G
• rs200020595
• NM_206808.5:c.50C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/22 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. A17T) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
CLYBL	NM_206808.5	c.50C>G	p.Ala17Gly	missense_variant	Exon 1 of 9	ENST00000339105.9	NP_996531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLYBL	ENST00000339105.9	c.50C>G	p.Ala17Gly	missense_variant	Exon 1 of 9	1	NM_206808.5	ENSP00000342991.4

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

African (AFR) AF: 0.00 AC: 0 AN: 27034

American (AMR) AF: 0.00 AC: 0 AN: 29172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23384

East Asian (EAS) AF: 0.00 AC: 0 AN: 29304

South Asian (SAS) AF: 0.00 AC: 0 AN: 72942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4042

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054146

Other (OTH) AF: 0.0000181 AC: 1 AN: 55270

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
PhyloP100		-0.039
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
PromoterAI		-0.053	Neutral
Varity_R		0.040
gMVP		0.47
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs200020595; hg19: chr13-100258999;