Variant 15-51094681-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 ENST00000327536.5(TNFAIP8L3):c.179C>G(p.Pro60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,188,966 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TNFAIP8L3
ENST00000327536.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.965

Variant links:

Genes affected

TNFAIP8L3 (HGNC:20620): (TNF alpha induced protein 8 like 3) Predicted to enable phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Predicted to be involved in several processes, including inositol lipid-mediated signaling; positive regulation of intracellular signal transduction; and positive regulation of phosphatidylinositol 3-kinase activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNFAIP8L3 links:

MIR4713HG (HGNC:53124): (MIR4713 host gene)

MIR4713HG links:

Genome browser will be placed here

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=0.057272643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNFAIP8L3	NM_001311175.2 linkuse as main transcript	c.-86C>G		5_prime_UTR_variant	1/2	ENST00000637513.2	NP_001298104.1
MIR4713HG	NR_146310.1 linkuse as main transcript	n.194+57000G>C		intron_variant, non_coding_transcript_variant
TNFAIP8L3	NM_207381.4 linkuse as main transcript	c.179C>G	p.Pro60Arg	missense_variant	2/3		NP_997264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TNFAIP8L3	ENST00000327536.5 linkuse as main transcript	c.179C>G	p.Pro60Arg	missense_variant	2/3	1		ENSP00000328016
TNFAIP8L3	ENST00000637513.2 linkuse as main transcript	c.-86C>G		5_prime_UTR_variant	1/2	1	NM_001311175.2	ENSP00000489743	P1
MIR4713HG	ENST00000559909.1 linkuse as main transcript	n.194+57000G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1042774

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

496816

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:

0.000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000334

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71128

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 11, 2022

The c.179C>G (p.P60R) alteration is located in exon 2 (coding exon 2) of the TNFAIP8L3 gene. This alteration results from a C to G substitution at nucleotide position 179, causing the proline (P) at amino acid position 60 to be replaced by an arginine (R). 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

0.089

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.9

DANN

Benign

0.87

DEOGEN2

Benign

0.061

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.28

M_CAP

Benign

0.0068

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

0.22

REVEL

Benign

0.018

Sift

Benign

0.061

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.12

MutPred

0.42

Gain of MoRF binding (P = 4e-04);

MVP

0.055

MPC

0.25

ClinPred

0.061

GERP RS

-6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.038

gMVP

0.040

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