7-27785253-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006024.7(TAX1BP1):c.703G>A(p.Glu235Lys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAX1BP1 NM_006024.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.05

Genes affected

TAX1BP1 (HGNC:11575): (Tax1 binding protein 1) This gene encodes a HTLV-1 tax1 binding protein. The encoded protein interacts with TNFAIP3, and inhibits TNF-induced apoptosis by mediating the TNFAIP3 anti-apoptotic activity. Degradation of this protein by caspase-3-like family proteins is associated with apoptosis induced by TNF. This protein may also have a role in the inhibition of inflammatory signaling pathways. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAX1BP1	NM_006024.7	c.703G>A	p.Glu235Lys	missense_variant	6/17	ENST00000396319.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAX1BP1	ENST00000396319.7	c.703G>A	p.Glu235Lys	missense_variant	6/17	1	NM_006024.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.703G>A (p.E235K) alteration is located in exon 6 (coding exon 5) of the TAX1BP1 gene. This alteration results from a G to A substitution at nucleotide position 703, causing the glutamic acid (E) at amino acid position 235 to be replaced by a lysine (K). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M;M;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Benign	0.27	T;T;T;T;T
Polyphen		1.0	D;D;.;.;D
Vest4		0.83
MutPred		0.84		Gain of ubiquitination at E235 (P = 0.0094);Gain of ubiquitination at E235 (P = 0.0094);.;Gain of ubiquitination at E235 (P = 0.0094);Gain of ubiquitination at E235 (P = 0.0094);
MVP		0.73
MPC		0.82
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.80
gMVP		0.58

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: chr7-27824872; COSMIC: COSV55296307;