5-119393274-G-C

Position:

• chr5-119393274-G-C

Variant summary

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

The ENST00000504771.3(TNFAIP8):​c.490G>C​(p.Asp164His) 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: 33)
• Consequence: TNFAIP8 ENST00000504771.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

Genes affected

TNFAIP8 (HGNC:17260): (TNF alpha induced protein 8) Enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process. Involved in positive regulation of apoptotic process. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2779602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP8	NM_014350.4	c.490G>C	p.Asp164His	missense_variant	2/2	ENST00000504771.3	NP_055165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP8	ENST00000504771.3	c.490G>C	p.Asp164His	missense_variant	2/2	1	NM_014350.4	ENSP00000422245

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jul 19, 2022

The c.490G>C (p.D164H) alteration is located in exon 2 (coding exon 2) of the TNFAIP8 gene. This alteration results from a G to C substitution at nucleotide position 490, causing the aspartic acid (D) at amino acid position 164 to be replaced by a histidine (H). 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	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;.;T;T;T
Eigen	Benign	0.042
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D;D;.;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	.;.;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D
REVEL	Benign	0.088
Sift	Benign	0.032	D;T;D;D;D
Sift4G	Uncertain	0.026	.;D;D;D;D
Polyphen		0.0010	B;.;B;B;.
Vest4		0.16
MutPred		0.78		.;.;Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;
MVP		0.53
MPC		0.32
ClinPred		0.93	D
GERP RS		3.0
Varity_R		0.23
gMVP		0.58

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: chr5-118728969;