Variant 20-44051315-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001098797.2(TOX2):c.421A>G(p.Met141Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00608 in 1,607,400 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 63 hom. )

Consequence

TOX2
NM_001098797.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

TOX2 (HGNC:16095): (TOX high mobility group box family member 2) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TOX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005722612).

BP6

Variant 20-44051315-A-G is Benign according to our data. Variant chr20-44051315-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 769471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00612 (8906/1455204) while in subpopulation MID AF= 0.034 (195/5740). AF 95% confidence interval is 0.0301. There are 63 homozygotes in gnomad4_exome. There are 4557 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX2	NM_001098797.2 linkuse as main transcript	c.421A>G	p.Met141Val	missense_variant	4/9	ENST00000341197.9	NP_001092267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9 linkuse as main transcript	c.421A>G	p.Met141Val	missense_variant	4/9	2	NM_001098797.2	ENSP00000344724	P4	Q96NM4-4

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.00310

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.00703

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00708

AC:

1742

AN:

246158

Hom.:

AF XY:

0.00743

AC XY:

990

AN XY:

133224

show subpopulations

Gnomad AFR exome

AF:

0.000927

Gnomad AMR exome

AF:

0.00573

Gnomad ASJ exome

AF:

0.0398

Gnomad EAS exome

AF:

0.00328

Gnomad SAS exome

AF:

0.00628

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.00708

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.00612

AC:

8906

AN:

1455204

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

4557

AN XY:

722702

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00658

Gnomad4 ASJ exome

AF:

0.0385

Gnomad4 EAS exome

AF:

0.00205

Gnomad4 SAS exome

AF:

0.00697

Gnomad4 FIN exome

AF:

0.00141

Gnomad4 NFE exome

AF:

0.00549

Gnomad4 OTH exome

AF:

0.00914

GnomAD4 genome

AF:

0.00574

AC:

873

AN:

152196

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.00291

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00703

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00825

Hom.:

Bravo

AF:

0.00617

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00671

AC:

815

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.00987

EpiControl

AF:

0.0109

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 23, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.037

.;.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.012

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;.;D;D

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

.;.;.;L

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.012

D;D;D;D

Sift4G

Uncertain

0.039

D;T;T;T

Polyphen

0.33

.;.;.;B

Vest4

0.72

MVP

0.42

MPC

0.59

ClinPred

0.015

GERP RS

5.6

Varity_R

0.23

gMVP

0.57

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