NM_014729.3:c.103-60814A>G

Variant names:

• chr8-59020822-T-C
• rs746867
• NM_014729.3:c.103-60814A>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.103-60814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,116 control chromosomes in the GnomAD database, including 3,686 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 0.21 (3686 hom., cov: 31)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.103-60814A>G		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.103-60814A>G		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32519 AN: 151998 Hom.: 3689 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.214 AC: 32528 AN: 152116 Hom.: 3686 Cov.: 31 AF XY: 0.215 AC XY: 16003 AN XY: 74390

African (AFR) AF: 0.277 AC: 11485 AN: 41474

American (AMR) AF: 0.223 AC: 3407 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1555 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4810

European-Finnish (FIN) AF: 0.182 AC: 1923 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11636 AN: 67998

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.187 Hom.: 7578

Bravo AF: 0.222

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.86
PhyloP100		-0.29
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: rs746867; hg19: chr8-59933381;