rs1305528873

Variant names:

• chr15-51094572-C-A
• rs1305528873
• NM_001311175.2:c.24G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-51094572-C-A
• chr15-51094572-C-G
• chr15-51094572-C-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.24G>T​(p.Gln8His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TNFAIP8L3 NM_001311175.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• 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=0.09983453).

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.24G>T	p.Gln8His	missense	Exon 1 of 2	NP_001298104.1	A0A1B0GTK8
	TNFAIP8L3	NM_207381.4		c.288G>T	p.Gln96His	missense	Exon 2 of 3	NP_997264.2	Q5GJ75
	MIR4713HG	NR_146310.1		n.194+56891C>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.24G>T	p.Gln8His	missense	Exon 1 of 2	ENSP00000489743.1	A0A1B0GTK8
	TNFAIP8L3	ENST00000327536.5	TSL:1	c.288G>T	p.Gln96His	missense	Exon 2 of 3	ENSP00000328016.5	Q5GJ75
	MIR4713HG	ENST00000559909.1	TSL:4	n.194+56891C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351048 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 667636

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27730

American (AMR) AF: 0.0000297 AC: 1 AN: 33722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23890

East Asian (EAS) AF: 0.00 AC: 0 AN: 29664

South Asian (SAS) AF: 0.00 AC: 0 AN: 76632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5392

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063016

Other (OTH) AF: 0.00 AC: 0 AN: 55988

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.092
Sift	Benign	0.063	T
Sift4G	Uncertain	0.038	D
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.064		Gain of glycosylation at S91 (P = 0.0961)
MVP		0.076
MPC		0.20
ClinPred		0.26	T
GERP RS		2.8
PromoterAI		-0.034	Neutral
Varity_R		0.15
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1305528873; hg19: chr15-51386769;