rs778088994

Variant names:

• chr13-99863054-C-G
• rs778088994
• NM_206808.5:c.502C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-99863054-C-G
• chr13-99863054-C-T

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.502C>G​(p.Pro168Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. P168S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLYBL NM_206808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77
• 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]

ENSG00000286757 (HGNC:):

CLYBL-AS3 (HGNC:56191): (CLYBL antisense RNA 3)

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=0.18601686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLYBL	NM_206808.5	c.502C>G	p.Pro168Ala	missense_variant	Exon 4 of 9	ENST00000339105.9	NP_996531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLYBL	ENST00000339105.9	c.502C>G	p.Pro168Ala	missense_variant	Exon 4 of 9	1	NM_206808.5	ENSP00000342991.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247638 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.52
DEOGEN2	Benign	0.026	T;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.12	N;N;.
PhyloP100		5.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.18	.;N;N
REVEL	Benign	0.14
Sift	Benign	0.46	.;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.026	B;B;.
Vest4		0.64
MutPred		0.53		Gain of catalytic residue at V170 (P = 2e-04);Gain of catalytic residue at V170 (P = 2e-04);.;
MVP		0.39
ClinPred		0.48	T
GERP RS		5.4
Varity_R		0.46
gMVP		0.64
Mutation Taster		=51/49	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

Other links and lift over

dbSNP: rs778088994; hg19: chr13-100515308;