6-137871382-G-C

Position:

• chr6-137871382-G-C

Variant summary

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

The NM_001270508.2(TNFAIP3):​c.155G>C​(p.Arg52Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFAIP3 NM_001270508.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.90

Genes affected

TNFAIP3 (HGNC:11896): (TNF alpha induced protein 3) This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]

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=0.39018792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP3	NM_001270508.2	c.155G>C	p.Arg52Thr	missense_variant	2/9	ENST00000612899.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.155G>C	p.Arg52Thr	missense_variant	2/9	5	NM_001270508.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.155G>C (p.R52T) alteration is located in exon 2 (coding exon 1) of the TNFAIP3 gene. This alteration results from a G to C substitution at nucleotide position 155, causing the arginine (R) at amino acid position 52 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T;T;T;.;.;T;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L;.;L;.;.;.;.;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.30	T;T;T;T;T;T;T;T;T
Polyphen		0.99	D;.;D;.;.;.;.;.;.
Vest4		0.64
MutPred		0.49		Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);Loss of MoRF binding (P = 0.0749);
MVP		0.60
MPC		1.2
ClinPred		0.70	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.61
gMVP		0.62

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: chr6-138192519;