rs746103477

Variant names:

• chr16-52439718-G-C
• NM_001080430.4:c.1238C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-52439718-G-C
• chr16-52439718-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080430.4(TOX3):​c.1238C>G​(p.Ala413Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A413D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOX3 NM_001080430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.68

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.135748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.1238C>G	p.Ala413Gly	missense_variant	Exon 7 of 7	ENST00000219746.14	NP_001073899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.1238C>G	p.Ala413Gly	missense_variant	Exon 7 of 7	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.1223C>G	p.Ala408Gly	missense_variant	Exon 8 of 8	2		ENSP00000385705.3
TOX3	ENST00000566696.1	n.1702C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.043
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.30	T;T
Polyphen		0.084	.;B
Vest4		0.23
MutPred		0.23		.;Loss of stability (P = 0.1157);
MVP		0.043
MPC		0.38
ClinPred		0.65	D
GERP RS		4.8
Varity_R		0.12
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-52473630;