Variant 7-102457591-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017621.4(ALKBH4):c.712G>A(p.Ala238Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,604,806 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ALKBH4
NM_017621.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.894

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.120051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKBH4	NM_017621.4 link	c.712G>A	p.Ala238Thr	missense_variant	3/3	ENST00000292566.4	NP_060091.1	Q9NXW9-1
ALKBH4	XM_005250464.4 link	c.493G>A	p.Ala165Thr	missense_variant	3/3		XP_005250521.1	Q9NXW9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ALKBH4	ENST00000292566.4 link	c.712G>A	p.Ala238Thr	missense_variant	3/3	1	NM_017621.4	ENSP00000292566.3	Q9NXW9-1
ALKBH4	ENST00000490528.1 link	n.*492G>A		non_coding_transcript_exon_variant	3/3	2		ENSP00000420362.1	Q9NXW9-2
ALKBH4	ENST00000490528.1 link	n.*492G>A		3_prime_UTR_variant	3/3	2		ENSP00000420362.1	Q9NXW9-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000254

AC:

AN:

235946

Hom.:

AF XY:

0.0000232

AC XY:

AN XY:

129294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1452492

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

722830

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 27, 2024

The c.712G>A (p.A238T) 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 712, causing the alanine (A) at amino acid position 238 to be replaced by a threonine (T). 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

0.091

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.60

M_CAP

Benign

0.020

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.54

REVEL

Benign

0.023

Sift

Benign

0.054

Sift4G

Benign

0.37

Polyphen

0.27

Vest4

0.034

MutPred

0.50

Gain of glycosylation at A238 (P = 0.0121);

MVP

0.23

MPC

0.30

ClinPred

0.11

GERP RS

2.0

Varity_R

0.023

gMVP

0.66

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