Genetic Variant TNIP2:p.Arg345Pro (chr4-2742513-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024309.4(TNIP2):c.1034G>C(p.Arg345Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R345Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TNIP2
NM_024309.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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=0.22254872).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNIP2	NM_024309.4	MANE Select	c.1034G>C	p.Arg345Pro	missense	Exon 6 of 6	NP_077285.3
TNIP2	NM_001292016.2		c.785G>C	p.Arg262Pro	missense	Exon 5 of 5	NP_001278945.1	D6RGJ2
TNIP2	NM_001161527.2		c.713G>C	p.Arg238Pro	missense	Exon 6 of 6	NP_001154999.1	Q8NFZ5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNIP2	ENST00000315423.12	TSL:1 MANE Select	c.1034G>C	p.Arg345Pro	missense	Exon 6 of 6	ENSP00000321203.7	Q8NFZ5-1
TNIP2	ENST00000892917.1		c.1046G>C	p.Arg349Pro	missense	Exon 6 of 6	ENSP00000562976.1
TNIP2	ENST00000892919.1		c.1025G>C	p.Arg342Pro	missense	Exon 6 of 6	ENSP00000562978.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1431762

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32592

American (AMR)

AF:

0.00

AC:

AN:

42230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24988

East Asian (EAS)

AF:

0.00

AC:

AN:

38538

South Asian (SAS)

AF:

0.00

AC:

AN:

83268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1092822

Other (OTH)

AF:

0.00

AC:

AN:

59030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.3

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.65

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.69

M_CAP

Benign

0.035

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.7

PhyloP100

0.084

PrimateAI

Benign

0.16

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.19

Sift

Benign

0.21

Sift4G

Uncertain

0.0040

Polyphen

0.74

Vest4

0.33

MutPred

0.31

Loss of MoRF binding (P = 0.008)

MVP

0.55

MPC

0.98

ClinPred

0.86

GERP RS

-3.1

Varity_R

0.20

gMVP

0.46

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over