rs1235035286

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-2742378-C-A
• chr4-2742378-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024309.4(TNIP2):​c.1169G>T​(p.Gly390Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,608,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNIP2 NM_024309.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10591015).

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>T	p.Gly390Val	missense	Exon 6 of 6	NP_077285.3
	TNIP2	NM_001292016.2		c.920G>T	p.Gly307Val	missense	Exon 5 of 5	NP_001278945.1	D6RGJ2
	TNIP2	NM_001161527.2		c.848G>T	p.Gly283Val	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>T	p.Gly390Val	missense	Exon 6 of 6	ENSP00000321203.7	Q8NFZ5-1
	TNIP2	ENST00000892917.1		c.1181G>T	p.Gly394Val	missense	Exon 6 of 6	ENSP00000562976.1
	TNIP2	ENST00000892919.1		c.1160G>T	p.Gly387Val	missense	Exon 6 of 6	ENSP00000562978.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456214 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 724114

African (AFR) AF: 0.00 AC: 0 AN: 33224

American (AMR) AF: 0.00 AC: 0 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.00 AC: 0 AN: 85440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109022

Other (OTH) AF: 0.00 AC: 0 AN: 60096

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

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	Benign	0.093
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.8
DANN	Benign	0.97
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.18
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.034
Sift	Benign	0.044	D
Sift4G	Uncertain	0.037	D
Polyphen		0.87	P
Vest4		0.067
MutPred		0.17		Loss of glycosylation at P386 (P = 0.015)
MVP		0.59
MPC		0.43
ClinPred		0.49	T
GERP RS		-0.21
Varity_R		0.090
gMVP		0.26
Mutation Taster		=87/13	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;