Variant rs41281112 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BS1_SupportingBS2

The NM_206808.5(CLYBL):c.775C>T(p.Arg259*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,613,646 control chromosomes in the GnomAD database, including 708 homozygotes. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.023 ( 61 hom., cov: 32)

Exomes 𝑓: 0.027 ( 647 hom. )

Consequence

CLYBL
NM_206808.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.00

Variant links:

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]

CLYBL links:

ENSG00000286757 (HGNC:):

ENSG00000286757 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP5

Variant 13-99866380-C-T is Pathogenic according to our data. Variant chr13-99866380-C-T is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0226 (3447/152250) while in subpopulation EAS AF= 0.043 (223/5184). AF 95% confidence interval is 0.0384. There are 61 homozygotes in gnomad4. There are 1749 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLYBL	NM_206808.5 linkuse as main transcript	c.775C>T	p.Arg259*	stop_gained	6/9	ENST00000339105.9	NP_996531.1	Q8N0X4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLYBL	ENST00000339105.9 linkuse as main transcript	c.775C>T	p.Arg259*	stop_gained	6/9	1	NM_206808.5	ENSP00000342991.4		Q8N0X4-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3446

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00526

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.0283

AC:

7097

AN:

250828

Hom.:

121

AF XY:

0.0280

AC XY:

3794

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.00554

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0497

Gnomad EAS exome

AF:

0.0491

Gnomad SAS exome

AF:

0.0235

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0332

GnomAD4 exome

AF:

0.0268

AC:

39223

AN:

1461396

Hom.:

647

Cov.:

AF XY:

0.0268

AC XY:

19470

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00508

Gnomad4 AMR exome

AF:

0.0290

Gnomad4 ASJ exome

AF:

0.0471

Gnomad4 EAS exome

AF:

0.0451

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.0349

Gnomad4 NFE exome

AF:

0.0260

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0226

AC:

3447

AN:

152250

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1749

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00527

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.0430

Gnomad4 SAS

AF:

0.0245

Gnomad4 FIN

AF:

0.0369

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0264

Hom.:

104

Bravo

AF:

0.0217

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0226

AC:

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0283

AC:

243

ExAC

AF:

0.0273

AC:

3315

EpiCase

AF:

0.0224

EpiControl

AF:

0.0251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Benign

0.96

Eigen

Benign

0.097

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.60

Vest4

0.31

GERP RS

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over