Variant 14-21492858-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000448790.7(TOX4):c.1242A>C(p.Gln414His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,342 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 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TOX4
ENST00000448790.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.51

Variant links:

Genes affected

TOX4 (HGNC:20161): (TOX high mobility group box family member 4) Predicted to enable chromatin DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in chromatin. Part of PTW/PP1 phosphatase complex. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

TOX4 links:

Genome browser will be placed here

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=0.06998557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX4	NM_014828.4 linkuse as main transcript	c.1242A>C	p.Gln414His	missense_variant	7/9	ENST00000448790.7	NP_055643.1
TOX4	NM_001303523.2 linkuse as main transcript	c.1173A>C	p.Gln391His	missense_variant	6/8		NP_001290452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX4	ENST00000448790.7 linkuse as main transcript	c.1242A>C	p.Gln414His	missense_variant	7/9	1	NM_014828.4	ENSP00000393080	P1	O94842-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000680

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

Nov 13, 2023

The c.1242A>C (p.Q414H) alteration is located in exon 7 (coding exon 7) of the TOX4 gene. This alteration results from a A to C substitution at nucleotide position 1242, causing the glutamine (Q) at amino acid position 414 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.61

DANN

Benign

0.78

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.30

.;N

REVEL

Benign

0.075

Sift

Benign

0.12

.;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0040

B;B

Vest4

0.47

MutPred

0.31

Gain of catalytic residue at P412 (P = 0.0057);Gain of catalytic residue at P412 (P = 0.0057);

MVP

0.18

ClinPred

0.14

GERP RS

-7.5

Varity_R

0.066

gMVP

0.53

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