NM_206808.5:c.38C>G

Variant names:

• chr13-99606733-C-G
• rs759290602
• NM_206808.5:c.38C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_206808.5(CLYBL):​c.38C>G​(p.Ala13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,336,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 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. A13V) 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: -0.733
• 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]

ENSG00000307597 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLYBL	NM_206808.5	c.38C>G	p.Ala13Gly	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.38C>G	p.Ala13Gly	missense_variant	Exon 1 of 9	1	NM_206808.5	ENSP00000342991.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.48e-7 AC: 1 AN: 1336124 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 659330

African (AFR) AF: 0.00 AC: 0 AN: 27056

American (AMR) AF: 0.00 AC: 0 AN: 29788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23500

East Asian (EAS) AF: 0.00 AC: 0 AN: 29566

South Asian (SAS) AF: 0.00 AC: 0 AN: 73330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4104

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1057206

Other (OTH) AF: 0.00 AC: 0 AN: 55512

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	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.050	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.49	.;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L
PhyloP100		-0.73
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.23	N;N;N
REVEL	Benign	0.019
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.023	B;B;B
Vest4		0.32
MutPred		0.35		Gain of catalytic residue at A13 (P = 0.0236);Gain of catalytic residue at A13 (P = 0.0236);Gain of catalytic residue at A13 (P = 0.0236);
MVP		0.061
ClinPred		0.15	T
GERP RS		0.35
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.083
gMVP		0.41
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs759290602; hg19: chr13-100258987;