rs775057322

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-99606742-C-T
• chr13-99606742-C-A
• chr13-99606742-C-G

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>T​(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,331,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CLYBL NM_206808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.114489436).

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.47C>T	p.Ala16Val	missense	Exon 1 of 9	NP_996531.1	Q8N0X4-1
	CLYBL	NM_001393356.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 9	NP_001380285.1	Q8N0X4-1
	CLYBL	NM_001393357.1		c.47C>T	p.Ala16Val	missense	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.47C>T	p.Ala16Val	missense	Exon 1 of 9	ENSP00000342991.4	Q8N0X4-1
	CLYBL	ENST00000933047.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 10	ENSP00000603106.1
	CLYBL	ENST00000898531.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 9	ENSP00000568590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000150 AC: 20 AN: 1331502 Hom.: 0 Cov.: 35 AF XY: 0.0000137 AC XY: 9 AN XY: 656920

African (AFR) AF: 0.0000371 AC: 1 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: 29324

South Asian (SAS) AF: 0.0000137 AC: 1 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: 0.0000171 AC: 18 AN: 1054394

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.054
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.044
Sift	Benign	0.28	T
Sift4G	Benign	0.36	T
Polyphen		0.0040	B
Vest4		0.33
MutPred		0.44		Loss of disorder (P = 0.0212)
MVP		0.20
ClinPred		0.51	D
GERP RS		1.6
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.037
gMVP		0.55
Mutation Taster		=94/6	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: rs775057322; hg19: chr13-100258996;