chr4-2744891-C-A

Variant names:

• chr4-2744891-C-A
• rs768831983
• NM_024309.4:c.712G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024309.4(TNIP2):​c.712G>T​(p.Val238Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: TNIP2 NM_024309.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024309.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP2	NM_024309.4	MANE Select	c.712G>T	p.Val238Leu	missense	Exon 4 of 6	NP_077285.3
	TNIP2	NM_001161527.2		c.391G>T	p.Val131Leu	missense	Exon 4 of 6	NP_001154999.1	Q8NFZ5-2
	TNIP2	NM_001292016.2		c.658-385G>T		intron	N/A	NP_001278945.1	D6RGJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP2	ENST00000315423.12	TSL:1 MANE Select	c.712G>T	p.Val238Leu	missense	Exon 4 of 6	ENSP00000321203.7	Q8NFZ5-1
	TNIP2	ENST00000892917.1		c.724G>T	p.Val242Leu	missense	Exon 4 of 6	ENSP00000562976.1
	TNIP2	ENST00000892919.1		c.703G>T	p.Val235Leu	missense	Exon 4 of 6	ENSP00000562978.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461046 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726694

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111506

Other (OTH) AF: 0.0000497 AC: 3 AN: 60370

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.27		Gain of glycosylation at Y237 (P = 0.0025)
MVP		0.78
MPC		1.0
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.35
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs768831983; hg19: chr4-2746618;