20-44003061-A-T

Variant names:

• chr20-44003061-A-T
• rs6017239
• NM_001098797.2:c.166-3486A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098797.2(TOX2):​c.166-3486A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,192 control chromosomes in the GnomAD database, including 567 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.057 (567 hom., cov: 31)
• Consequence: TOX2 NM_001098797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.166-3486A>T		intron_variant	Intron 2 of 8	ENST00000341197.9	NP_001092267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9	c.166-3486A>T		intron_variant	Intron 2 of 8	2	NM_001098797.2	ENSP00000344724.3
TOX2	ENST00000372999.5	c.40-3486A>T		intron_variant	Intron 3 of 9	1		ENSP00000362090.1
TOX2	ENST00000358131.5	c.193-3486A>T		intron_variant	Intron 2 of 7	2		ENSP00000350849.5
TOX2	ENST00000423191.6	c.40-3486A>T		intron_variant	Intron 2 of 8	2		ENSP00000390278.1

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8706 AN: 152074 Hom.: 559 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0369

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0575 AC: 8750 AN: 152192 Hom.: 567 Cov.: 31 AF XY: 0.0545 AC XY: 4054 AN XY: 74404

African (AFR) AF: 0.161 AC: 6677 AN: 41500

American (AMR) AF: 0.0271 AC: 415 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4822

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10606

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0202 AC: 1374 AN: 68012

Other (OTH) AF: 0.0365 AC: 77 AN: 2108

Alfa AF: 0.0381 Hom.: 32

Bravo AF: 0.0643

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.62
DANN	Benign	0.76
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6017239; hg19: chr20-42631701;