Variant 5-119393295-T-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_014350.4(TNFAIP8):c.511T>A(p.Leu171Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000743 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

TNFAIP8
NM_014350.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

TNFAIP8 (HGNC:17260): (TNF alpha induced protein 8) Enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process. Involved in positive regulation of apoptotic process. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNFAIP8 links:

Genome browser will be placed here

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=0.3013299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP8	NM_014350.4 linkuse as main transcript	c.511T>A	p.Leu171Met	missense_variant	2/2	ENST00000504771.3	NP_055165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP8	ENST00000504771.3 linkuse as main transcript	c.511T>A	p.Leu171Met	missense_variant	2/2	1	NM_014350.4	ENSP00000422245		O95379-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152238

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:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

249158

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135170

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:

0.00101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

727130

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:

0.00117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74500

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:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000190

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

May 24, 2023

The c.511T>A (p.L171M) alteration is located in exon 2 (coding exon 2) of the TNFAIP8 gene. This alteration results from a T to A substitution at nucleotide position 511, causing the leucine (L) at amino acid position 171 to be replaced by a methionine (M). 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

0.26

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;.;T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.8

.;.;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Uncertain

0.011

.;D;D;D;D

Polyphen

1.0

D;.;D;D;.

Vest4

0.77

MutPred

0.85

.;.;Loss of stability (P = 0.2035);Loss of stability (P = 0.2035);.;

MVP

0.47

MPC

0.94

ClinPred

0.25

GERP RS

3.6

Varity_R

0.32

gMVP

0.59

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