13-99606749-G-T

Variant names:

• chr13-99606749-G-T
• NM_206808.5:c.54G>T
• CLYBL p.Leu18Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_206808.5(CLYBL):​c.54G>T​(p.Leu18Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000751 in 1,331,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CLYBL NM_206808.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206808.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLYBL	NM_206808.5	MANE Select	c.54G>T	p.Leu18Leu	synonymous	Exon 1 of 9	NP_996531.1	Q8N0X4-1
	CLYBL	NM_001393356.1		c.54G>T	p.Leu18Leu	synonymous	Exon 1 of 9	NP_001380285.1	Q8N0X4-1
	CLYBL	NM_001393357.1		c.54G>T	p.Leu18Leu	synonymous	Exon 1 of 8	NP_001380286.1	Q8N0X4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLYBL	ENST00000339105.9	TSL:1 MANE Select	c.54G>T	p.Leu18Leu	synonymous	Exon 1 of 9	ENSP00000342991.4	Q8N0X4-1
	CLYBL	ENST00000933047.1		c.54G>T	p.Leu18Leu	synonymous	Exon 1 of 10	ENSP00000603106.1
	CLYBL	ENST00000898531.1		c.54G>T	p.Leu18Leu	synonymous	Exon 1 of 9	ENSP00000568590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331324 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 656772

African (AFR) AF: 0.00 AC: 0 AN: 26984

American (AMR) AF: 0.0000344 AC: 1 AN: 29088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23352

East Asian (EAS) AF: 0.00 AC: 0 AN: 29292

South Asian (SAS) AF: 0.00 AC: 0 AN: 73112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4040

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054380

Other (OTH) AF: 0.00 AC: 0 AN: 55290

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		3.7
PromoterAI		0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-100259003;