rs10504283

Variant names:

• chr8-59064251-T-C
• rs10504283
• NM_014729.3:c.102+54635A>G

Variant summary

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

The NM_014729.3(TOX):​c.102+54635A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 152,320 control chromosomes in the GnomAD database, including 212 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 0.037 (212 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 1 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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.102+54635A>G		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.102+54635A>G		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5678 AN: 152202 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0374 AC: 5701 AN: 152320 Hom.: 212 Cov.: 32 AF XY: 0.0363 AC XY: 2705 AN XY: 74482

African (AFR) AF: 0.0957 AC: 3977 AN: 41544

American (AMR) AF: 0.0188 AC: 287 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4830

European-Finnish (FIN) AF: 0.0186 AC: 198 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 936 AN: 68034

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0241 Hom.: 23

Bravo AF: 0.0398

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.085
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: rs10504283; hg19: chr8-59976810;