Variant 20-43914910-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 NM_001098797.2(TOX2):c.19C>T(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,140,702 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 0.00032 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

TOX2
NM_001098797.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.916

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 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=0.042494595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TOX2	NM_001098797.2 linkuse as main transcript	c.19C>T	p.Pro7Ser	missense_variant	1/9	ENST00000341197.9	NP_001092267.1
TOX2	XM_047440563.1 linkuse as main transcript	c.19C>T	p.Pro7Ser	missense_variant	1/8		XP_047296519.1
TOX2	XM_047440565.1 linkuse as main transcript	c.19C>T	p.Pro7Ser	missense_variant	1/7		XP_047296521.1
TOX2	XM_047440561.1 linkuse as main transcript	c.-233C>T		5_prime_UTR_variant	1/10		XP_047296517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9 linkuse as main transcript	c.19C>T	p.Pro7Ser	missense_variant	1/9	2	NM_001098797.2	ENSP00000344724	P4	Q96NM4-4

Frequencies

GnomAD3 genomes

AF:

0.000317

AC:

AN:

148494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000196

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:

0.000585

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000730

AC:

AN:

2740

Hom.:

AF XY:

0.000621

AC XY:

AN XY:

1610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00113

AC:

1123

AN:

992208

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

510

AN XY:

472950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000441

Gnomad4 FIN exome

AF:

0.0000744

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.000577

GnomAD4 genome

AF:

0.000317

AC:

AN:

148494

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

AN XY:

72350

show subpopulations

Gnomad4 AFR

AF:

0.000196

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:

0.000585

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.000412

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 15, 2021

The c.19C>T (p.P7S) alteration is located in exon 1 (coding exon 1) of the TOX2 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a serine (S). 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

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.84

REVEL

Benign

0.060

Sift

Benign

0.098

Sift4G

Benign

0.28

Vest4

0.15

MVP

0.19

MPC

0.83

ClinPred

0.28

GERP RS

2.3

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