Variant 7-102457507-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000292566.4(ALKBH4):c.796G>A(p.Val266Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

ALKBH4
ENST00000292566.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.991

Variant links:

Genes affected

ALKBH4 (HGNC:21900): (alkB homolog 4, lysine demethylase) Enables 2-oxoglutarate-dependent dioxygenase activity and actin binding activity. Involved in actomyosin structure organization; cleavage furrow ingression; and protein demethylation. Located in contractile ring and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ALKBH4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0323413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKBH4	NM_017621.4 linkuse as main transcript	c.796G>A	p.Val266Ile	missense_variant	3/3	ENST00000292566.4	NP_060091.1	Q9NXW9-1
ALKBH4	XM_005250464.4 linkuse as main transcript	c.577G>A	p.Val193Ile	missense_variant	3/3		XP_005250521.1	Q9NXW9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ALKBH4	ENST00000292566.4 linkuse as main transcript	c.796G>A	p.Val266Ile	missense_variant	3/3	1	NM_017621.4	ENSP00000292566.3	Q9NXW9-1
ALKBH4	ENST00000490528.1 linkuse as main transcript	n.*576G>A		non_coding_transcript_exon_variant	3/3	2		ENSP00000420362.1	Q9NXW9-2
ALKBH4	ENST00000490528.1 linkuse as main transcript	n.*576G>A		3_prime_UTR_variant	3/3	2		ENSP00000420362.1	Q9NXW9-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000197

AC:

AN:

248840

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1460924

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.796G>A (p.V266I) alteration is located in exon 3 (coding exon 3) of the ALKBH4 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the valine (V) at amino acid position 266 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.78

M_CAP

Benign

0.021

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.66

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.28

REVEL

Benign

0.12

Sift

Benign

0.32

Sift4G

Benign

0.65

Polyphen

0.63

Vest4

0.068

MutPred

0.72

Gain of helix (P = 0.0854);

MVP

0.14

MPC

0.32

ClinPred

0.062

GERP RS

4.0

Varity_R

0.025

gMVP

0.55

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

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