Variant chr14-103127115-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006291.4(TNFAIP2):c.346G>A(p.Glu116Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,101,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TNFAIP2
NM_006291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

TNFAIP2 (HGNC:11895): (TNF alpha induced protein 2) This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. The expression of this gene was shown to be induced by retinoic acid in a cell line expressing a oncogenic version of the retinoic acid receptor alpha fusion protein, which suggested that this gene may be a retinoic acid target gene in acute promyelocytic leukemia. [provided by RefSeq, Jul 2008]

TNFAIP2 links:

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ACMG classification

Classification made for transcript

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=0.37747943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP2	NM_006291.4 link	c.346G>A	p.Glu116Lys	missense_variant	3/12	ENST00000560869.6	NP_006282.2	Q03169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP2	ENST00000560869.6 link	c.346G>A	p.Glu116Lys	missense_variant	3/12	5	NM_006291.4	ENSP00000452634.2		Q03169

Frequencies

GnomAD3 genomes

AF:

0.0000476

AC:

AN:

147060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000106

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

108

AN:

954560

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

452374

show subpopulations

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:

0.000129

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000476

AC:

AN:

147060

Hom.:

Cov.:

AF XY:

0.0000419

AC XY:

AN XY:

71566

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000106

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.346G>A (p.E116K) alteration is located in exon 2 (coding exon 2) of the TNFAIP2 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the glutamic acid (E) at amino acid position 116 to be replaced by a lysine (K). 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

0.25

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.66

.;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.73

P;P

Vest4

0.25

MutPred

0.74

Gain of MoRF binding (P = 0.0045);Gain of MoRF binding (P = 0.0045);

MVP

0.33

MPC

2.6

ClinPred

0.74

GERP RS

1.9

Varity_R

0.068

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over