chr4-2744886-C-G

Position:

• chr4-2744886-C-G

Variant summary

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

The ENST00000315423.12(TNIP2):​c.717G>C​(p.Arg239Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R239T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNIP2 ENST00000315423.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.548

Genes affected

TNIP2 (HGNC:19118): (TNFAIP3 interacting protein 2) This gene encodes a protein which acts as an inhibitor of NFkappaB activation. The encoded protein is also involved in MAP/ERK signaling pathway in specific cell types. It may be involved in apoptosis of endothelial cells. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the X chromosome.[provided by RefSeq, May 2014]

TNIP2 (HGNC:):

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
TNIP2	NM_024309.4	c.717G>C	p.Arg239Ser	missense_variant	4/6	ENST00000315423.12	NP_077285.3
TNIP2	NM_001161527.2	c.396G>C	p.Arg132Ser	missense_variant	4/6		NP_001154999.1
TNIP2	NM_001292016.2	c.658-380G>C		intron_variant			NP_001278945.1
TNIP2	XM_047416149.1	c.337-380G>C		intron_variant			XP_047272105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP2	ENST00000315423.12	c.717G>C	p.Arg239Ser	missense_variant	4/6	1	NM_024309.4	ENSP00000321203.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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

Jan 23, 2024

The c.717G>C (p.R239S) alteration is located in exon 4 (coding exon 4) of the TNIP2 gene. This alteration results from a G to C substitution at nucleotide position 717, causing the arginine (R) at amino acid position 239 to be replaced by a serine (S). 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	0.41
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;T
Eigen	Benign	0.099
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	.;M
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.065
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.90	.;P
Vest4		0.44
MutPred		0.38		.;Gain of glycosylation at Y237 (P = 0.0025);
MVP		0.77
MPC		0.78
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.53
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-2746613;