6-137871250-A-G

Position:

• chr6-137871250-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270508.2(TNFAIP3):​c.23A>G​(p.Gln8Arg) 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. 14/21 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: TNFAIP3 NM_001270508.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1410808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP3	NM_001270508.2	c.23A>G	p.Gln8Arg	missense_variant	2/9	ENST00000612899.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.23A>G	p.Gln8Arg	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

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;.;T;T;.;.;T;T;T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;.;.;L;.;.;.;.;.;.
MutationTaster	Benign	0.82	D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.0	.;D;N;N;N;.;.;.;.;.
REVEL	Benign	0.037
Sift	Benign	0.57	.;.;T;T;T;.;.;.;.;.
Sift4G	Benign	0.41	T;T;T;T;T;T;T;T;T;T
Polyphen		0.043	B;.;.;B;.;.;.;.;.;.
Vest4		0.27
MutPred		0.38		Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);Gain of MoRF binding (P = 0.0131);
MVP		0.55
MPC		0.61
ClinPred		0.91	D
GERP RS		1.1
Varity_R		0.12
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs1582884850; hg19: chr6-138192387;