5-119393356-A-C

Position:

• chr5-119393356-A-C

Variant summary

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

The NM_014350.4(TNFAIP8):​c.572A>C​(p.Lys191Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNFAIP8 NM_014350.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP8	NM_014350.4	c.572A>C	p.Lys191Thr	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.572A>C	p.Lys191Thr	missense_variant	2/2	1	NM_014350.4	ENSP00000422245.1

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

Dec 21, 2023

The c.572A>C (p.K191T) alteration is located in exon 2 (coding exon 2) of the TNFAIP8 gene. This alteration results from a A to C substitution at nucleotide position 572, causing the lysine (K) at amino acid position 191 to be replaced by a threonine (T). 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	0.25
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;.;T;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T;.;T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	.;.;M;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.048	D;T;T;T;T
Sift4G	Benign	0.11	.;T;T;T;T
Polyphen		0.35	B;.;B;B;.
Vest4		0.69
MutPred		0.58		.;.;Loss of ubiquitination at K191 (P = 0.013);Loss of ubiquitination at K191 (P = 0.013);.;
MVP		0.63
MPC		0.54
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.35
gMVP		0.51

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: chr5-118729051;