Variant 11-107504819-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_138775.3(ALKBH8):c.1834G>T(p.Gly612Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,551,738 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 91 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 65 hom. )

Consequence

ALKBH8
NM_138775.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.865

Variant links:

Genes affected

ALKBH8 (HGNC:25189): (alkB homolog 8, tRNA methyltransferase) Enables tRNA (uracil) methyltransferase activity; tRNA binding activity; and zinc ion binding activity. Involved in cellular response to DNA damage stimulus; tRNA methylation; and tRNA wobble uridine modification. Located in cytosol and nuclear body. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

ALKBH8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003430456).

BP6

Variant 11-107504819-C-A is Benign according to our data. Variant chr11-107504819-C-A is described in ClinVar as [Benign]. Clinvar id is 3043881.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALKBH8	NM_138775.3 link	c.1834G>T	p.Gly612Cys	missense_variant	Exon 12 of 12	ENST00000428149.7	NP_620130.2	Q96BT7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALKBH8	ENST00000428149.7 link	c.1834G>T	p.Gly612Cys	missense_variant	Exon 12 of 12	1	NM_138775.3	ENSP00000415885.2		Q96BT7-1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2690

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0615

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00412

AC:

649

AN:

157446

Hom.:

AF XY:

0.00328

AC XY:

273

AN XY:

83166

show subpopulations

Gnomad AFR exome

AF:

0.0661

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000360

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.00183

AC:

2556

AN:

1399550

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1113

AN XY:

690278

show subpopulations

Gnomad4 AFR exome

AF:

0.0619

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.00480

GnomAD4 genome

AF:

0.0177

AC:

2697

AN:

152188

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1287

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0616

Gnomad4 AMR

AF:

0.00635

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00341

Hom.:

Bravo

AF:

0.0207

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0658

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.00713

AC:

180

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ALKBH8-related disorder

Benign:1

Nov 13, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.66

.;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.066

Sift

Benign

0.090

T;T;T

Sift4G

Uncertain

0.029

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.26

MVP

0.27

MPC

0.041

ClinPred

0.018

GERP RS

3.4

Varity_R

0.076

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over