chr8-58973753-T-A

Variant names:

• chr8-58973753-T-A
• rs12545204
• NM_014729.3:c.103-13745A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014729.3(TOX):​c.103-13745A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,066 control chromosomes in the GnomAD database, including 40,581 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 0.72 (40581 hom., cov: 31)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.805 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.103-13745A>T		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.103-13745A>T		intron	N/A	ENSP00000354842.1	O94900
	TOX	ENST00000890858.1		c.103-34209A>T		intron	N/A	ENSP00000560917.1
	TOX	ENST00000966264.1		c.103-13745A>T		intron	N/A	ENSP00000636323.1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110122 AN: 151948 Hom.: 40561 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.725 AC: 110190 AN: 152066 Hom.: 40581 Cov.: 31 AF XY: 0.728 AC XY: 54093 AN XY: 74334

African (AFR) AF: 0.590 AC: 24449 AN: 41446

American (AMR) AF: 0.688 AC: 10497 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2761 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3754 AN: 5172

South Asian (SAS) AF: 0.826 AC: 3982 AN: 4820

European-Finnish (FIN) AF: 0.842 AC: 8911 AN: 10586

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.785 AC: 53400 AN: 67984

Other (OTH) AF: 0.717 AC: 1515 AN: 2114

Alfa AF: 0.745 Hom.: 5039

Bravo AF: 0.702

Asia WGS AF: 0.760 AC: 2642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		0.28
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: rs12545204; hg19: chr8-59886312;