TOX3 p.Val128Leu

Variant names:

• chr16-52463960-C-A
• NM_001080430.4:c.382G>T
• TOX3 p.Val128Leu

Your query was ambiguous. Multiple possible variants found:

• chr16-52463960-C-A
• chr16-52463960-C-G
• chr16-52463958-CAC-TAA
• chr16-52463958-CAC-AAG
• chr16-52463958-CAC-GAG
• chr16-52463958-CAC-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080430.4(TOX3):​c.382G>T​(p.Val128Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TOX3 NM_001080430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695
• Publications: 0 publications found

Genes affected

TOX3 (HGNC:11972): (TOX high mobility group box family member 3) The protein encoded by this gene contains an HMG-box, indicating that it may be involved in bending and unwinding of DNA and alteration of chromatin structure. The C-terminus of the encoded protein is glutamine-rich due to CAG repeats in the coding sequence. A minor allele of this gene has been implicated in an elevated risk of breast cancer. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11869529).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080430.4. 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
	TOX3	NM_001080430.4	MANE Select	c.382G>T	p.Val128Leu	missense	Exon 3 of 7	NP_001073899.2	O15405-1
	TOX3	NM_001146188.2		c.367G>T	p.Val123Leu	missense	Exon 4 of 8	NP_001139660.1	O15405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX3	ENST00000219746.14	TSL:2 MANE Select	c.382G>T	p.Val128Leu	missense	Exon 3 of 7	ENSP00000219746.9	O15405-1
	TOX3	ENST00000912163.1		c.382G>T	p.Val128Leu	missense	Exon 3 of 8	ENSP00000582222.1
	TOX3	ENST00000873102.1		c.379G>T	p.Val127Leu	missense	Exon 3 of 7	ENSP00000543161.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.2
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.69
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.14
Sift	Benign	0.65	T
Sift4G	Benign	0.82	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-52497872;