4-2742378-C-T

Variant names:

• chr4-2742378-C-T
• rs1235035286
• NM_024309.4:c.1169G>A

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.1169G>A​(p.Gly390Asp) 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. G390V) 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: -0.180
• 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=0.051641107).

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.1169G>A	p.Gly390Asp	missense	Exon 6 of 6	NP_077285.3
	TNIP2	NM_001292016.2		c.920G>A	p.Gly307Asp	missense	Exon 5 of 5	NP_001278945.1	D6RGJ2
	TNIP2	NM_001161527.2		c.848G>A	p.Gly283Asp	missense	Exon 6 of 6	NP_001154999.1	Q8NFZ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP2	ENST00000315423.12	TSL:1 MANE Select	c.1169G>A	p.Gly390Asp	missense	Exon 6 of 6	ENSP00000321203.7	Q8NFZ5-1
	TNIP2	ENST00000892917.1		c.1181G>A	p.Gly394Asp	missense	Exon 6 of 6	ENSP00000562976.1
	TNIP2	ENST00000892919.1		c.1160G>A	p.Gly387Asp	missense	Exon 6 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: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.1
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	L
PhyloP100		-0.18
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.0070
Sift	Benign	0.046	D
Sift4G	Benign	0.34	T
Polyphen		0.013	B
Vest4		0.051
MutPred		0.15		Loss of glycosylation at P386 (P = 0.015)
MVP		0.49
MPC		0.43
ClinPred		0.039	T
GERP RS		-0.21
Varity_R		0.039
gMVP		0.16
Mutation Taster		=86/14	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: rs1235035286; hg19: chr4-2744105;