rs310362

Variant names:

• chr8-59013059-C-T
• rs310362
• NM_014729.3:c.103-53051G>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.103-53051G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,068 control chromosomes in the GnomAD database, including 21,275 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 (21275 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.103-53051G>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.103-53051G>A		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75310 AN: 151952 Hom.: 21255 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.495 AC: 75343 AN: 152068 Hom.: 21275 Cov.: 32 AF XY: 0.501 AC XY: 37285 AN XY: 74350

African (AFR) AF: 0.212 AC: 8808 AN: 41458

American (AMR) AF: 0.557 AC: 8519 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2950 AN: 5172

South Asian (SAS) AF: 0.538 AC: 2587 AN: 4808

European-Finnish (FIN) AF: 0.724 AC: 7667 AN: 10586

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41629 AN: 67970

Other (OTH) AF: 0.488 AC: 1028 AN: 2108

Alfa AF: 0.566 Hom.: 46440

Bravo AF: 0.470

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.28
PhyloP100		-1.1
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: rs310362; hg19: chr8-59925618;