8-59034864-C-T

Variant names:

• chr8-59034864-C-T
• rs9693712
• NM_014729.3:c.103-74856G>A

Variant summary

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

The NM_014729.3(TOX):​c.103-74856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,074 control chromosomes in the GnomAD database, including 20,440 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 0.50 (20440 hom., cov: 33)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 5 publications found

Genes affected

TOX (HGNC:18988): (thymocyte selection associated high mobility group box) The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[provided by RefSeq, Apr 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.103-74856G>A		intron_variant	Intron 1 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.103-74856G>A		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75681 AN: 151954 Hom.: 20433 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.498 AC: 75721 AN: 152074 Hom.: 20440 Cov.: 33 AF XY: 0.497 AC XY: 36949 AN XY: 74326

African (AFR) AF: 0.297 AC: 12295 AN: 41458

American (AMR) AF: 0.485 AC: 7419 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2303 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1581 AN: 5182

South Asian (SAS) AF: 0.562 AC: 2703 AN: 4810

European-Finnish (FIN) AF: 0.625 AC: 6609 AN: 10568

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41060 AN: 67984

Other (OTH) AF: 0.493 AC: 1039 AN: 2106

Alfa AF: 0.565 Hom.: 18841

Bravo AF: 0.478

Asia WGS AF: 0.483 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0090
DANN	Benign	0.56
PhyloP100		-2.4
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: rs9693712; hg19: chr8-59947423;