8-59045582-A-G

Variant names:

• chr8-59045582-A-G
• rs172652
• NM_014729.3:c.102+73304T>C

Variant summary

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

The NM_014729.3(TOX):​c.102+73304T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,124 control chromosomes in the GnomAD database, including 55,897 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 0.86 (55897 hom., cov: 30)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.102+73304T>C		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.102+73304T>C		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129976 AN: 152006 Hom.: 55863 Cov.: 30

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.855 AC: 130067 AN: 152124 Hom.: 55897 Cov.: 30 AF XY: 0.858 AC XY: 63837 AN XY: 74392

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.842

Alfa AF: 0.853 Hom.: 6440

Bravo AF: 0.850

Asia WGS AF: 0.953 AC: 3313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.63

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: rs172652; hg19: chr8-59958141;