7-27787575-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006024.7(TAX1BP1):c.1010G>C(p.Arg337Thr) 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. 12/21 in silico tools predict a benign 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: 2.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3738484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAX1BP1	NM_006024.7	c.1010G>C	p.Arg337Thr	missense_variant	8/17	ENST00000396319.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAX1BP1	ENST00000396319.7	c.1010G>C	p.Arg337Thr	missense_variant	8/17	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

Apr 13, 2022

The c.1010G>C (p.R337T) alteration is located in exon 8 (coding exon 7) of the TAX1BP1 gene. This alteration results from a G to C substitution at nucleotide position 1010, causing the arginine (R) at amino acid position 337 to be replaced by a threonine (T). 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	0.20
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;.;D;D;D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;.;.;L
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D;D;D;D;D
Sift4G	Uncertain	0.059	T;T;T;D;D
Polyphen		0.76	P;P;.;.;P
Vest4		0.39
MutPred		0.61		Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);.;Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);
MVP		0.50
MPC		0.49
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-27827194;