chr2-151370175-G-T

Position:

• chr2-151370175-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007115.4(TNFAIP6):​c.550G>T​(p.Asp184Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TNFAIP6 NM_007115.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46

Genes affected

TNFAIP6 (HGNC:11898): (TNF alpha induced protein 6) The protein encoded by this gene is a secretory protein that contains a hyaluronan-binding domain, and thus is a member of the hyaluronan-binding protein family. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable complex with inter-alpha-inhibitor (I alpha I), and thus enhance the serine protease inhibitory activity of I alpha I, which is important in the protease network associated with inflammation. This gene can be induced by proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-1. Enhanced levels of this protein are found in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis.[provided by RefSeq, Dec 2010]

TNFAIP6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2971148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP6	NM_007115.4	c.550G>T	p.Asp184Tyr	missense_variant	4/6	ENST00000243347.5	NP_009046.2
TNFAIP6	XM_047445635.1	c.550G>T	p.Asp184Tyr	missense_variant	4/6		XP_047301591.1
LOC101929319	NR_110248.1	n.306+2620C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP6	ENST00000243347.5	c.550G>T	p.Asp184Tyr	missense_variant	4/6	1	NM_007115.4	ENSP00000243347.3
TNFAIP6	ENST00000460812.1	n.232G>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.550G>T (p.D184Y) alteration is located in exon 4 (coding exon 4) of the TNFAIP6 gene. This alteration results from a G to T substitution at nucleotide position 550, causing the aspartic acid (D) at amino acid position 184 to be replaced by a tyrosine (Y). 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	0.26
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.12
Sift	Benign	0.043	D
Sift4G	Uncertain	0.025	D
Polyphen		0.0010	B
Vest4		0.40
MutPred		0.66		Loss of disorder (P = 0.0761);
MVP		0.60
MPC		0.31
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.76
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-152226689;