8-58828331-T-G

Variant names:

• chr8-58828331-T-G
• rs826730
• NM_014729.3:c.925-1429A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014729.3(TOX):​c.925-1429A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,022 control chromosomes in the GnomAD database, including 38,057 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 0.70 (38057 hom., cov: 33)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.925-1429A>C		intron_variant	Intron 5 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.925-1429A>C		intron_variant	Intron 5 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106251 AN: 151904 Hom.: 38023 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.699 AC: 106335 AN: 152022 Hom.: 38057 Cov.: 33 AF XY: 0.707 AC XY: 52534 AN XY: 74278

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.723

Alfa AF: 0.545 Hom.: 1137

Bravo AF: 0.690

Asia WGS AF: 0.864 AC: 2999 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.29

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: rs826730; hg19: chr8-59740890;