rs775057322

Variant names:

• chr13-99606742-C-A
• rs775057322
• NM_206808.5:c.47C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-99606742-C-A
• chr13-99606742-C-G
• chr13-99606742-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.47C>A​(p.Ala16Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A16V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLYBL NM_206808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• 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: 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=0.11792448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLYBL	NM_206808.5	c.47C>A	p.Ala16Glu	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.47C>A	p.Ala16Glu	missense_variant	Exon 1 of 9	1	NM_206808.5	ENSP00000342991.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1331502 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 656922

African (AFR) AF: 0.00 AC: 0 AN: 26934

American (AMR) AF: 0.00 AC: 0 AN: 29188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23414

East Asian (EAS) AF: 0.00 AC: 0 AN: 29322

South Asian (SAS) AF: 0.00 AC: 0 AN: 73108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4050

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054396

Other (OTH) AF: 0.00 AC: 0 AN: 55276

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.052	T;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.70
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.51	.;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L;L
PhyloP100		0.054
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.48	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.50	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.45
MVP		0.16
ClinPred		0.16	T
GERP RS		1.6
PromoterAI		0.0060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.073
gMVP		0.68
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775057322; hg19: chr13-100258996;