chr15-51058357-T-A

Variant names:

• chr15-51058357-T-A
• rs372237970
• NM_001311175.2:c.139A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001311175.2(TNFAIP8L3):​c.139A>T​(p.Met47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M47V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFAIP8L3 NM_001311175.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15619871).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001311175.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP8L3	NM_001311175.2	MANE Select	c.139A>T	p.Met47Leu	missense	Exon 2 of 2	NP_001298104.1	A0A1B0GTK8
	TNFAIP8L3	NM_207381.4		c.403A>T	p.Met135Leu	missense	Exon 3 of 3	NP_997264.2	Q5GJ75
	MIR4713HG	NR_146310.1		n.194+20676T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP8L3	ENST00000637513.2	TSL:1 MANE Select	c.139A>T	p.Met47Leu	missense	Exon 2 of 2	ENSP00000489743.1	A0A1B0GTK8
	TNFAIP8L3	ENST00000327536.5	TSL:1	c.403A>T	p.Met135Leu	missense	Exon 3 of 3	ENSP00000328016.5	Q5GJ75
	TNFAIP8L3	ENST00000649177.1		c.1A>T	p.Met1?	initiator_codon	Exon 2 of 2	ENSP00000498365.1	A0A494C051

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.73	N
PhyloP100		3.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.077
Sift	Benign	0.52	T
Sift4G	Benign	0.32	T
Polyphen		0.042	B
Vest4		0.28
MutPred		0.36		Loss of MoRF binding (P = 0.0877)
MVP		0.067
MPC		0.24
ClinPred		0.51	D
GERP RS		4.2
Varity_R		0.32
gMVP		0.19
Mutation Taster		=67/33	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: rs372237970; hg19: chr15-51350554;