Variant 11-107510892-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138775.3(ALKBH8):c.1432A>G(p.Thr478Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,551,280 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 31 hom. )

Consequence

ALKBH8
NM_138775.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.74

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007777363).

BP6

Variant 11-107510892-T-C is Benign according to our data. Variant chr11-107510892-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2672483.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKBH8	NM_138775.3 linkuse as main transcript	c.1432A>G	p.Thr478Ala	missense_variant	11/12	ENST00000428149.7	NP_620130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALKBH8	ENST00000428149.7 linkuse as main transcript	c.1432A>G	p.Thr478Ala	missense_variant	11/12	1	NM_138775.3	ENSP00000415885	P1	Q96BT7-1

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

513

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0286

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00499

AC:

777

AN:

155690

Hom.:

AF XY:

0.00444

AC XY:

366

AN XY:

82358

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.00374

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00220

Gnomad SAS exome

AF:

0.0000442

Gnomad FIN exome

AF:

0.0318

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00251

AC:

3511

AN:

1398992

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1657

AN XY:

689956

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.00325

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.000784

Gnomad4 SAS exome

AF:

0.0000632

Gnomad4 FIN exome

AF:

0.0327

Gnomad4 NFE exome

AF:

0.00146

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.00337

AC:

513

AN:

152288

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

324

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0286

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00132

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.00408

AC:

104

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

ALKBH8: BS2 -

ALKBH8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

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

0.23

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;D

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-0.40

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.78

MVP

0.73

MPC

0.064

ClinPred

0.042

GERP RS

5.1

Varity_R

0.58

gMVP

0.70

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

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