chr8-58812942-A-C

Variant names:

• chr8-58812942-A-C
• rs3109904
• NM_014729.3:c.1392+2396T>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.1392+2396T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,096 control chromosomes in the GnomAD database, including 5,981 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 0.27 (5981 hom., cov: 33)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.1392+2396T>G		intron_variant	Intron 7 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.1392+2396T>G		intron_variant	Intron 7 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41140 AN: 151978 Hom.: 5976 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.271 AC: 41165 AN: 152096 Hom.: 5981 Cov.: 33 AF XY: 0.274 AC XY: 20359 AN XY: 74348

African (AFR) AF: 0.373 AC: 15459 AN: 41482

American (AMR) AF: 0.239 AC: 3653 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1781 AN: 5158

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4818

European-Finnish (FIN) AF: 0.252 AC: 2669 AN: 10580

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14121 AN: 67988

Other (OTH) AF: 0.272 AC: 576 AN: 2116

Alfa AF: 0.232 Hom.: 4570

Bravo AF: 0.272

Asia WGS AF: 0.367 AC: 1275 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	6.0
DANN	Benign	0.73
PhyloP100		0.061
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: rs3109904; hg19: chr8-59725501;