17-28339592-G-T

Position:

• chr17-28339592-G-T

Variant summary

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

The NM_021137.5(TNFAIP1):​c.71G>T​(p.Gly24Val) 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. 15/21 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: 3.03

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=0.19664109).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP1	NM_021137.5	c.71G>T	p.Gly24Val	missense_variant	2/7	ENST00000226225.7
TNFAIP1	XM_017024993.3	c.71G>T	p.Gly24Val	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP1	ENST00000226225.7	c.71G>T	p.Gly24Val	missense_variant	2/7	1	NM_021137.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000617 Hom.: 0

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

Oct 26, 2022

The c.71G>T (p.G24V) alteration is located in exon 2 (coding exon 1) of the TNFAIP1 gene. This alteration results from a G to T substitution at nucleotide position 71, causing the glycine (G) at amino acid position 24 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	Benign	0.069
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.00087
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.039	D;D;D
Polyphen		0.0030	.;B;.
Vest4		0.22
MVP		0.44
MPC		0.61
ClinPred		0.55	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.46

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: chr17-26666618; COSMIC: COSV56876003; COSMIC: COSV56876003;