NM_001311175.2:c.-86C>T

Variant names:

• chr15-51094681-G-A
• rs777218814
• NM_001311175.2:c.-86C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001311175.2(TNFAIP8L3):​c.-86C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,189,078 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 0.000055 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TNFAIP8L3 NM_001311175.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.965
• Publications: 0 publications found

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]

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

ENSG00000304751 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0338794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP8L3	NM_001311175.2	c.-86C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000637513.2	NP_001298104.1
TNFAIP8L3	NM_001311175.2	c.-86C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000637513.2	NP_001298104.1
TNFAIP8L3	NM_207381.4	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3		NP_997264.2
MIR4713HG	NR_146310.1	n.194+57000G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L3	ENST00000637513.2	c.-86C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_001311175.2	ENSP00000489743.1
TNFAIP8L3	ENST00000637513.2	c.-86C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_001311175.2	ENSP00000489743.1

Frequencies

GnomAD3 genomes AF: 0.0000547 AC: 8 AN: 146192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 814 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 15 AN: 1042774 Hom.: 0 Cov.: 30 AF XY: 0.0000121 AC XY: 6 AN XY: 496816

African (AFR) AF: 0.000191 AC: 4 AN: 20900

American (AMR) AF: 0.00 AC: 0 AN: 6620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11816

East Asian (EAS) AF: 0.00 AC: 0 AN: 22370

South Asian (SAS) AF: 0.000377 AC: 8 AN: 21220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2682

European-Non Finnish (NFE) AF: 0.00000334 AC: 3 AN: 898486

Other (OTH) AF: 0.00 AC: 0 AN: 40064

GnomAD4 genome AF: 0.0000547 AC: 8 AN: 146304 Hom.: 0 Cov.: 32 AF XY: 0.0000702 AC XY: 5 AN XY: 71244

African (AFR) AF: 0.000147 AC: 6 AN: 40936

American (AMR) AF: 0.00 AC: 0 AN: 14740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.000420 AC: 2 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65774

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000211 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.179C>T (p.P60L) alteration is located in exon 2 (coding exon 2) of the TNFAIP8L3 gene. This alteration results from a C to T substitution at nucleotide position 179, causing the proline (P) at amino acid position 60 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	0.16
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.91
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.96
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.0060
Sift	Benign	1.0	T
Sift4G	Benign	0.069	T
Polyphen		0.0	B
Vest4		0.092
MutPred		0.40		Gain of helix (P = 0.0022);
MVP		0.092
MPC		0.23
ClinPred		0.035	T
GERP RS		-6.0
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.018
gMVP		0.056
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs777218814; hg19: chr15-51386878;