8-58877651-G-C

Variant names:

• chr8-58877651-G-C
• rs2594953
• NM_014729.3:c.412-25846C>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.412-25846C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,044 control chromosomes in the GnomAD database, including 16,273 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 0.43 (16273 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.412-25846C>G		intron_variant	Intron 3 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.412-25846C>G		intron_variant	Intron 3 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64617 AN: 151926 Hom.: 16237 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.426 AC: 64702 AN: 152044 Hom.: 16273 Cov.: 32 AF XY: 0.418 AC XY: 31093 AN XY: 74320

African (AFR) AF: 0.699 AC: 29003 AN: 41474

American (AMR) AF: 0.414 AC: 6329 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3464

East Asian (EAS) AF: 0.418 AC: 2152 AN: 5152

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2552 AN: 10574

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20728 AN: 67968

Other (OTH) AF: 0.398 AC: 840 AN: 2108

Alfa AF: 0.196 Hom.: 394

Bravo AF: 0.455

Asia WGS AF: 0.395 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		0.23
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: rs2594953; hg19: chr8-59790210;