rs2726599

Positions:

• chr8-58806137-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.*1610G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,896 control chromosomes in the GnomAD database, including 10,139 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 0.36 (10139 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TOX NM_014729.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX	NM_014729.3	c.*1610G>A		3_prime_UTR_variant	9/9	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.*1610G>A		3_prime_UTR_variant	9/9	1	NM_014729.3	ENSP00000354842	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54372 AN: 151776 Hom.: 10129 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.356

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.358 AC: 54407 AN: 151896 Hom.: 10139 Cov.: 32 AF XY: 0.357 AC XY: 26496 AN XY: 74238

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.353

Alfa AF: 0.380 Hom.: 15567

Bravo AF: 0.360

Asia WGS AF: 0.497 AC: 1724 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	1.5
DANN	Benign	0.37

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: rs2726599; hg19: chr8-59718696;