Variant 14-103127009-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006291.4(TNFAIP2):c.240G>C(p.Glu80Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,200,798 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 0.00042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

TNFAIP2
NM_006291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0120303035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP2	NM_006291.4 linkuse as main transcript	c.240G>C	p.Glu80Asp	missense_variant	3/12	ENST00000560869.6	NP_006282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP2	ENST00000560869.6 linkuse as main transcript	c.240G>C	p.Glu80Asp	missense_variant	3/12	5	NM_006291.4	ENSP00000452634	P1

Frequencies

GnomAD3 genomes

AF:

0.000424

AC:

AN:

150964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00357

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000355

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000704

AC:

AN:

5680

Hom.:

AF XY:

0.000543

AC XY:

AN XY:

3680

show subpopulations

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:

0.00704

Gnomad NFE exome

AF:

0.000430

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000320

AC:

336

AN:

1049726

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

154

AN XY:

504168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000886

Gnomad4 FIN exome

AF:

0.00432

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000330

GnomAD4 genome

AF:

0.000424

AC:

AN:

151072

Hom.:

Cov.:

AF XY:

0.000596

AC XY:

AN XY:

73820

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00357

Gnomad4 NFE

AF:

0.000355

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.000219

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

Jun 22, 2021

The c.240G>C (p.E80D) alteration is located in exon 2 (coding exon 2) of the TNFAIP2 gene. This alteration results from a G to C substitution at nucleotide position 240, causing the glutamic acid (E) at amino acid position 80 to be replaced by an aspartic acid (D). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.076

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.56

.;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.047

Sift

Benign

0.19

T;T

Sift4G

Uncertain

0.049

D;D

Polyphen

0.94

P;P

Vest4

0.086

MutPred

0.33

Gain of catalytic residue at P75 (P = 0.001);Gain of catalytic residue at P75 (P = 0.001);

MVP

0.46

MPC

2.3

ClinPred

0.056

GERP RS

3.1

Varity_R

0.18

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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