NM_014729.3:c.411+5750A>C

Variant names:

• chr8-58933552-T-G
• rs6997859
• NM_014729.3:c.411+5750A>C

Variant summary

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

The NM_014729.3(TOX):​c.411+5750A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 149,756 control chromosomes in the GnomAD database, including 10,404 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 0.37 (10404 hom., cov: 28)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 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.411+5750A>C		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.411+5750A>C		intron	N/A	ENSP00000354842.1	O94900
	TOX	ENST00000890858.1		c.345+5750A>C		intron	N/A	ENSP00000560917.1
	TOX	ENST00000966264.1		c.411+5750A>C		intron	N/A	ENSP00000636323.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 54677 AN: 149630 Hom.: 10403 Cov.: 28

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.365 AC: 54709 AN: 149756 Hom.: 10404 Cov.: 28 AF XY: 0.368 AC XY: 26892 AN XY: 73072

African (AFR) AF: 0.294 AC: 11960 AN: 40726

American (AMR) AF: 0.371 AC: 5580 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 848 AN: 3448

East Asian (EAS) AF: 0.618 AC: 3105 AN: 5022

South Asian (SAS) AF: 0.426 AC: 1959 AN: 4600

European-Finnish (FIN) AF: 0.416 AC: 4219 AN: 10138

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 25981 AN: 67508

Other (OTH) AF: 0.341 AC: 713 AN: 2088

Alfa AF: 0.178 Hom.: 355

Bravo AF: 0.357

Asia WGS AF: 0.425 AC: 1478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.036
DANN	Benign	0.51
PhyloP100		-1.6
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: rs6997859; hg19: chr8-59846111;