8-58924945-C-T

Position:

• chr8-58924945-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.411+14357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,984 control chromosomes in the GnomAD database, including 8,365 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 0.31 (8365 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX	NM_014729.3	c.411+14357G>A		intron_variant		ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.411+14357G>A		intron_variant		1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47320 AN: 151866 Hom.: 8359 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.311 AC: 47338 AN: 151984 Hom.: 8365 Cov.: 32 AF XY: 0.313 AC XY: 23275 AN XY: 74284

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.315

Alfa AF: 0.370 Hom.: 21585

Bravo AF: 0.291

Asia WGS AF: 0.281 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.65

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: rs1463142; hg19: chr8-59837504;