NM_014729.3:c.103-10760T>A

Variant names:

• chr8-58970768-A-T
• rs10283344
• NM_014729.3:c.103-10760T>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.103-10760T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,160 control chromosomes in the GnomAD database, including 36,915 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 0.68 (36915 hom., cov: 33)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.103-10760T>A		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.103-10760T>A		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103649 AN: 152042 Hom.: 36897 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.682 AC: 103712 AN: 152160 Hom.: 36915 Cov.: 33 AF XY: 0.684 AC XY: 50864 AN XY: 74394

African (AFR) AF: 0.466 AC: 19326 AN: 41480

American (AMR) AF: 0.666 AC: 10173 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2760 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3271 AN: 5184

South Asian (SAS) AF: 0.734 AC: 3539 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8913 AN: 10608

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53355 AN: 67994

Other (OTH) AF: 0.690 AC: 1458 AN: 2112

Alfa AF: 0.725 Hom.: 5081

Bravo AF: 0.657

Asia WGS AF: 0.649 AC: 2253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		-0.34
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: rs10283344; hg19: chr8-59883327;