19-4652245-C-G

Variant names:

Variant summary

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

The NM_152362.3(TNFAIP8L1):c.376C>G(p.Leu126Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000148 in 1,556,296 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 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TNFAIP8L1
NM_152362.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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 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=0.020608485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP8L1	NM_152362.3 link	c.376C>G	p.Leu126Val	missense_variant	Exon 2 of 2	ENST00000327473.9	NP_689575.2	Q8WVP5
TNFAIP8L1	NM_001167942.1 link	c.376C>G	p.Leu126Val	missense_variant	Exon 2 of 2		NP_001161414.1	Q8WVP5
TNFAIP8L1	XM_005259487.4 link	c.376C>G	p.Leu126Val	missense_variant	Exon 2 of 2		XP_005259544.1	Q8WVP5
TNFAIP8L1	XM_011527680.3 link	c.376C>G	p.Leu126Val	missense_variant	Exon 2 of 2		XP_011525982.1	Q8WVP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNFAIP8L1	ENST00000327473.9 link	c.376C>G	p.Leu126Val	missense_variant	Exon 2 of 2	1	NM_152362.3	ENSP00000331827.3	Q8WVP5
TNFAIP8L1	ENST00000536716.1 link	c.376C>G	p.Leu126Val	missense_variant	Exon 2 of 2	2		ENSP00000444215.1	Q8WVP5
MYDGF	ENST00000599761.5 link	c.184+7686G>C		intron_variant	Intron 3 of 3	3		ENSP00000469136.1	M0QXF7

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152246

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:

0.000962

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

GnomAD3 exomes

AF:

0.0000566

AC:

AN:

159124

Hom.:

AF XY:

0.0000573

AC XY:

AN XY:

87258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000736

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1403932

Hom.:

Cov.:

AF XY:

0.00000864

AC XY:

AN XY:

694308

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000495

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ExAC

AF:

0.0000605

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.376C>G (p.L126V) alteration is located in exon 2 (coding exon 1) of the TNFAIP8L1 gene. This alteration results from a C to G substitution at nucleotide position 376, causing the leucine (L) at amino acid position 126 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.12

T;T

Sift4G

Uncertain

0.044

D;D

Polyphen

0.90

P;P

Vest4

0.39

MutPred

0.63

Loss of stability (P = 0.3474);Loss of stability (P = 0.3474);

MVP

0.38

MPC

1.3

ClinPred

0.44

GERP RS

4.4

Varity_R

0.28

gMVP

0.63

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