14-21492761-C-A

Variant names:

• chr14-21492761-C-A
• NM_014828.4:c.1145C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014828.4. 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
	TOX4	NM_014828.4	MANE Select	c.1145C>A	p.Ser382Tyr	missense	Exon 7 of 9	NP_055643.1	O94842-1
	TOX4	NM_001303523.2		c.1076C>A	p.Ser359Tyr	missense	Exon 6 of 8	NP_001290452.1	O94842-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX4	ENST00000448790.7	TSL:1 MANE Select	c.1145C>A	p.Ser382Tyr	missense	Exon 7 of 9	ENSP00000393080.3	O94842-1
	TOX4	ENST00000911770.1		c.1145C>A	p.Ser382Tyr	missense	Exon 7 of 9	ENSP00000581829.1
	TOX4	ENST00000613569.4	TSL:5	c.1145C>A	p.Ser382Tyr	missense	Exon 8 of 10	ENSP00000477868.1	O94842-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.70	T
REVEL	Benign	0.24
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.78
MutPred		0.46		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
Mutation Taster		=80/20	polymorphism

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

hg19: chr14-21960920;