Variant 14-103126681-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006291.4(TNFAIP2):c.224C>T(p.Pro75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,405,494 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TNFAIP2
NM_006291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.92

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18205819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP2	NM_006291.4 linkuse as main transcript	c.224C>T	p.Pro75Leu	missense_variant	2/12	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.224C>T	p.Pro75Leu	missense_variant	2/12	5	NM_006291.4	ENSP00000452634	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

157912

Hom.:

AF XY:

0.0000353

AC XY:

AN XY:

84938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000792

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000334

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1405494

Hom.:

Cov.:

AF XY:

0.00000432

AC XY:

AN XY:

693720

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:

0.00000369

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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

Feb 14, 2023

The c.224C>T (p.P75L) alteration is located in exon 1 (coding exon 1) of the TNFAIP2 gene. This alteration results from a C to T substitution at nucleotide position 224, causing the proline (P) at amino acid position 75 to be replaced by a leucine (L). 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

0.078

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.9

DANN

Benign

0.90

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.079

Sift

Benign

0.043

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.97

D;D

Vest4

0.22

MutPred

0.35

Gain of catalytic residue at P76 (P = 0.0028);Gain of catalytic residue at P76 (P = 0.0028);

MVP

0.49

MPC

2.6

ClinPred

0.27

GERP RS

-8.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.055

gMVP

0.15

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