4-2744771-C-G

Variant names:

• chr4-2744771-C-G
• rs755542378
• NM_024309.4:c.832G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024309.4(TNIP2):​c.832G>C​(p.Val278Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V278M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNIP2 NM_024309.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06509167).

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.832G>C	p.Val278Leu	missense	Exon 4 of 6	NP_077285.3
	TNIP2	NM_001161527.2		c.511G>C	p.Val171Leu	missense	Exon 4 of 6	NP_001154999.1	Q8NFZ5-2
	TNIP2	NM_001292016.2		c.658-265G>C		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.832G>C	p.Val278Leu	missense	Exon 4 of 6	ENSP00000321203.7	Q8NFZ5-1
	TNIP2	ENST00000892917.1		c.844G>C	p.Val282Leu	missense	Exon 4 of 6	ENSP00000562976.1
	TNIP2	ENST00000892919.1		c.823G>C	p.Val275Leu	missense	Exon 4 of 6	ENSP00000562978.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.8
DANN	Benign	0.21
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.93	L
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.16
MutPred		0.16		Loss of glycosylation at K279 (P = 0.0778)
MVP		0.55
MPC		0.31
ClinPred		0.061	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.14
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs755542378; hg19: chr4-2746498;