chr13-99606708-C-T

Variant names:

• chr13-99606708-C-T
• rs570970577
• NM_206808.5:c.13C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_206808.5(CLYBL):​c.13C>T​(p.Leu5Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,494,290 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: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CLYBL NM_206808.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.366 with no splicing effect.

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.13C>T	p.Leu5Leu	synonymous	Exon 1 of 9	NP_996531.1	Q8N0X4-1
	CLYBL	NM_001393356.1		c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 9	NP_001380285.1	Q8N0X4-1
	CLYBL	NM_001393357.1		c.13C>T	p.Leu5Leu	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.13C>T	p.Leu5Leu	synonymous	Exon 1 of 9	ENSP00000342991.4	Q8N0X4-1
	CLYBL	ENST00000933047.1		c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 10	ENSP00000603106.1
	CLYBL	ENST00000898531.1		c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 9	ENSP00000568590.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151922 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.000481

GnomAD4 exome AF: 0.0000209 AC: 28 AN: 1342368 Hom.: 0 Cov.: 35 AF XY: 0.0000181 AC XY: 12 AN XY: 662542

African (AFR) AF: 0.00 AC: 0 AN: 27330

American (AMR) AF: 0.00 AC: 0 AN: 30894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23610

East Asian (EAS) AF: 0.00 AC: 0 AN: 29958

South Asian (SAS) AF: 0.00 AC: 0 AN: 74012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4208

European-Non Finnish (NFE) AF: 0.0000255 AC: 27 AN: 1060522

Other (OTH) AF: 0.0000179 AC: 1 AN: 55820

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151922 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67974

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		0.37
PromoterAI		-0.039	Neutral

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: rs570970577; hg19: chr13-100258962;