13-99648499-A-G

Variant names:

• chr13-99648499-A-G
• rs10508039
• NM_206808.5:c.62+41742A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206808.5(CLYBL):​c.62+41742A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,158 control chromosomes in the GnomAD database, including 6,160 homozygotes. 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 0.26 (6160 hom., cov: 32)
• Consequence: CLYBL NM_206808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLYBL	NM_206808.5	c.62+41742A>G		intron_variant	Intron 1 of 8	ENST00000339105.9	NP_996531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLYBL	ENST00000339105.9	c.62+41742A>G		intron_variant	Intron 1 of 8	1	NM_206808.5	ENSP00000342991.4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39039 AN: 152038 Hom.: 6161 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 39039 AN: 152158 Hom.: 6160 Cov.: 32 AF XY: 0.264 AC XY: 19598 AN XY: 74374

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.254

Alfa AF: 0.263 Hom.: 742

Bravo AF: 0.247

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs10508039; hg19: chr13-100300753;