15-51094649-C-G

Variant names:

• chr15-51094649-C-G
• rs746106215
• ENST00000327536.5:c.211G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000327536.5(TNFAIP8L3):​c.211G>C​(p.Glu71Gln) 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. E71K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNFAIP8L3 ENST00000327536.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035316944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP8L3	NM_001311175.2	c.-54G>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000637513.2	NP_001298104.1
TNFAIP8L3	NM_207381.4	c.211G>C	p.Glu71Gln	missense_variant	Exon 2 of 3		NP_997264.2
MIR4713HG	NR_146310.1	n.194+56968C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L3	ENST00000637513.2	c.-54G>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_001311175.2	ENSP00000489743.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.12
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.037
Sift	Benign	0.18	T
Sift4G	Benign	0.088	T
Polyphen		0.0060	B
Vest4		0.099
MutPred		0.091		Gain of MoRF binding (P = 0.1019);
MVP		0.030
MPC		0.22
ClinPred		0.092	T
GERP RS		-1.5
PromoterAI		0.0096	Neutral
Varity_R		0.042
gMVP		0.11

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: rs746106215; hg19: chr15-51386846;