8-58924945-C-T

Variant names:

• chr8-58924945-C-T
• rs1463142
• NM_014729.3:c.411+14357G>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.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
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014729.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX	NM_014729.3	MANE Select	c.411+14357G>A		intron	N/A	NP_055544.1	O94900

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX	ENST00000361421.2	TSL:1 MANE Select	c.411+14357G>A		intron	N/A	ENSP00000354842.1	O94900
	TOX	ENST00000890858.1		c.345+14357G>A		intron	N/A	ENSP00000560917.1
	TOX	ENST00000966264.1		c.411+14357G>A		intron	N/A	ENSP00000636323.1

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

African (AFR) AF: 0.156 AC: 6456 AN: 41454

American (AMR) AF: 0.293 AC: 4473 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1187 AN: 5168

South Asian (SAS) AF: 0.251 AC: 1206 AN: 4812

European-Finnish (FIN) AF: 0.471 AC: 4972 AN: 10556

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26332 AN: 67930

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.363 Hom.: 43607

Bravo AF: 0.291

Asia WGS AF: 0.281 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.65
PhyloP100		-1.3
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: rs1463142; hg19: chr8-59837504;