chr6-137878809-G-C

Variant names:

• chr6-137878809-G-C
• rs587778714
• NM_001270508.2:c.1364G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001270508.2(TNFAIP3):​c.1364G>C​(p.Gly455Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TNFAIP3 NM_001270508.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.092766434).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.1364G>C	p.Gly455Ala	missense_variant	Exon 7 of 9	ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.1364G>C	p.Gly455Ala	missense_variant	Exon 7 of 9	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250216 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135602

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461748 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727178

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000251 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.18
DEOGEN2	Benign	0.12	T;T;.;T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.91	D;.;T;D;D;D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.093	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;L;.;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.020	.;N;.;.;.;.
REVEL	Benign	0.10
Sift	Benign	1.0	.;T;.;.;.;.
Sift4G	Benign	0.57	T;T;T;T;T;T
Polyphen		0.039	B;B;.;.;.;.
Vest4		0.24
MutPred		0.057		Gain of glycosylation at P457 (P = 0.2224);Gain of glycosylation at P457 (P = 0.2224);Gain of glycosylation at P457 (P = 0.2224);Gain of glycosylation at P457 (P = 0.2224);Gain of glycosylation at P457 (P = 0.2224);Gain of glycosylation at P457 (P = 0.2224);
MVP		0.50
MPC		0.33
ClinPred		0.037	T
GERP RS		2.2
Varity_R		0.051
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: rs587778714; hg19: chr6-138199946; COSMIC: COSV105865125; COSMIC: COSV105865125;