NM_021137.5:c.535C>G

Variant names:

• chr17-28342263-C-G
• NM_021137.5:c.535C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021137.5(TNFAIP1):​c.535C>G​(p.Leu179Val) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFAIP1 NM_021137.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.417

Genes affected

TNFAIP1 (HGNC:11894): (TNF alpha induced protein 1) This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. Studies of a similar gene in mouse suggest that the expression of this gene is developmentally regulated in a tissue-specific manner. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24179775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP1	NM_021137.5	c.535C>G	p.Leu179Val	missense_variant	Exon 6 of 7	ENST00000226225.7	NP_066960.1
TNFAIP1	XM_017024993.3	c.535C>G	p.Leu179Val	missense_variant	Exon 6 of 7		XP_016880482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP1	ENST00000226225.7	c.535C>G	p.Leu179Val	missense_variant	Exon 6 of 7	1	NM_021137.5	ENSP00000226225.2
TNFAIP1	ENST00000544907.6	c.223C>G	p.Leu75Val	missense_variant	Exon 5 of 6	2		ENSP00000440749.2
TNFAIP1	ENST00000577535.1	c.223C>G	p.Leu75Val	missense_variant	Exon 4 of 4	3		ENSP00000466301.1
TNFAIP1	ENST00000583213.1	n.256C>G		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.535C>G (p.L179V) alteration is located in exon 6 (coding exon 5) of the TNFAIP1 gene. This alteration results from a C to G substitution at nucleotide position 535, causing the leucine (L) at amino acid position 179 to be replaced by a valine (V). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.8	.;M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.85	.;P;.
Vest4		0.66
MutPred		0.32		.;Loss of helix (P = 0.0444);.;
MVP		0.66
MPC		0.62
ClinPred		0.99	D
GERP RS		1.4
Varity_R		0.35
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26669289;