Variant 7-102457906-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017621.4(ALKBH4):c.397C>T(p.Arg133Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ALKBH4
NM_017621.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33089048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKBH4	NM_017621.4 linkuse as main transcript	c.397C>T	p.Arg133Trp	missense_variant	3/3	ENST00000292566.4	NP_060091.1
ALKBH4	XM_005250464.4 linkuse as main transcript	c.178C>T	p.Arg60Trp	missense_variant	3/3		XP_005250521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALKBH4	ENST00000292566.4 linkuse as main transcript	c.397C>T	p.Arg133Trp	missense_variant	3/3	1	NM_017621.4	ENSP00000292566	P1	Q9NXW9-1
ALKBH4	ENST00000490528.1 linkuse as main transcript	c.*177C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	2		ENSP00000420362		Q9NXW9-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

249766

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461084

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000768

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 17, 2023

The c.397C>T (p.R133W) alteration is located in exon 3 (coding exon 3) of the ALKBH4 gene. This alteration results from a C to T substitution at nucleotide position 397, causing the arginine (R) at amino acid position 133 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.029

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.22

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.15

MVP

0.68

MPC

0.67

ClinPred

0.67

GERP RS

4.7

Varity_R

0.21

gMVP

0.58

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