chr15-51094681-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: Not reported in ClinVar
• Conservation: PhyloP100: -0.965

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)

ACMG classification

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=0.0338794).

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

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

Gnomad4 AFR exome AF: 0.000191

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000377

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000334

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.000147

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000420

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.000211 AC: 2

ClinVar

Not reported in ClinVar

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
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.018
gMVP		0.056

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

Other links and lift over

dbSNP: rs777218814; hg19: chr15-51386878;