19-4652405-G-A

Position:

chr19-4652405-G-A

Variant summary

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

The NM_152362.3(TNFAIP8L1):c.536G>A(p.Arg179Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000651 in 1,536,794 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

TNFAIP8L1
NM_152362.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

TNFAIP8L1 (HGNC:28279): (TNF alpha induced protein 8 like 1) Enables identical protein binding activity. Predicted to be involved in negative regulation of TOR signaling. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNFAIP8L1 links:

MYDGF (HGNC:16948): (myeloid derived growth factor) The protein encoded by this gene was previously thought to support proliferation of lymphoid cells and was considered an interleukin. However, this activity has not been reproducible and the function of this protein is currently unknown. [provided by RefSeq, Jul 2008]

MYDGF links:

Genome browser will be placed here

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=0.24570653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP8L1	NM_152362.3 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2	ENST00000327473.9	NP_689575.2	Q8WVP5
TNFAIP8L1	NM_001167942.1 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2		NP_001161414.1	Q8WVP5
TNFAIP8L1	XM_005259487.4 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2		XP_005259544.1	Q8WVP5
TNFAIP8L1	XM_011527680.3 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2		XP_011525982.1	Q8WVP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFAIP8L1	ENST00000327473.9 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2	1	NM_152362.3	ENSP00000331827.3	Q8WVP5
TNFAIP8L1	ENST00000536716.1 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	2/2	2		ENSP00000444215.1	Q8WVP5
MYDGF	ENST00000599761.5 linkuse as main transcript	c.184+7526C>T		intron_variant		3		ENSP00000469136.1	M0QXF7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00000650

AC:

AN:

1384540

Hom.:

Cov.:

AF XY:

0.00000734

AC XY:

AN XY:

681586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000278

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:

0.00000652

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Dec 15, 2023

The c.536G>A (p.R179Q) alteration is located in exon 2 (coding exon 1) of the TNFAIP8L1 gene. This alteration results from a G to A substitution at nucleotide position 536, causing the arginine (R) at amino acid position 179 to be replaced by a glutamine (Q). 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

0.079

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.089

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.57

P;P

Vest4

0.053

MutPred

0.68

Loss of MoRF binding (P = 0.0755);Loss of MoRF binding (P = 0.0755);

MVP

0.11

MPC

1.1

ClinPred

0.46

GERP RS

3.3

Varity_R

0.099

gMVP

0.18

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