chr14-21492761-C-A

Variant summary

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

The NM_014828.4(TOX4):​c.1145C>A​(p.Ser382Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TOX4
NM_014828.4 missense

Scores

2
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09
Variant links:
Genes affected
TOX4 (HGNC:20161): (TOX high mobility group box family member 4) Predicted to enable chromatin DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in chromatin. Part of PTW/PP1 phosphatase complex. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOX4NM_014828.4 linkc.1145C>A p.Ser382Tyr missense_variant Exon 7 of 9 ENST00000448790.7 NP_055643.1 O94842-1
TOX4NM_001303523.2 linkc.1076C>A p.Ser359Tyr missense_variant Exon 6 of 8 NP_001290452.1 O94842-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOX4ENST00000448790.7 linkc.1145C>A p.Ser382Tyr missense_variant Exon 7 of 9 1 NM_014828.4 ENSP00000393080.3 O94842-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
67
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1145C>A (p.S382Y) alteration is located in exon 7 (coding exon 7) of the TOX4 gene. This alteration results from a C to A substitution at nucleotide position 1145, causing the serine (S) at amino acid position 382 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.062
T;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
.;T
M_CAP
Benign
0.0023
T
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Uncertain
0.70
T
REVEL
Benign
0.24
Sift4G
Uncertain
0.036
D;D
Polyphen
0.99
D;D
Vest4
0.78
MutPred
0.46
Gain of catalytic residue at Q383 (P = 7e-04);Gain of catalytic residue at Q383 (P = 7e-04);
MVP
0.36
ClinPred
0.86
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.68

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: chr14-21960920; API