rs61756235

chr6-137876122-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001270508.2(TNFAIP3):c.761G>A(p.Ser254Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TNFAIP3 NM_001270508.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1697312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP3	NM_001270508.2	c.761G>A	p.Ser254Asn	missense_variant	5/9	ENST00000612899.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.761G>A	p.Ser254Asn	missense_variant	5/9	5	NM_001270508.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461772 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727180

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.;T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.78	T;.;T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;L;.;.;.;.
MutationTaster	Benign	0.92	D
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		0.0070	B;B;.;.;.;.
Vest4		0.33
MutPred		0.49		Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
MVP		0.24
MPC		0.28
ClinPred		0.58	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.56

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: rs61756235; hg19: chr6-138197259; COSMIC: COSV52798522; COSMIC: COSV52798522;