rs9693712

Positions:

• chr8-59034864-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TOX	NM_014729.3	c.103-74856G>A		intron_variant		ENST00000361421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX	ENST00000361421.2	c.103-74856G>A		intron_variant		1	NM_014729.3	P1

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

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.493

Alfa AF: 0.567 Hom.: 15715

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

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

Other links and lift over

dbSNP: rs9693712; hg19: chr8-59947423;