chr2-151370027-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007115.4(TNFAIP6):ā€‹c.402G>Cā€‹(p.Glu134Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000596 in 1,611,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00032 ( 0 hom., cov: 32)
Exomes š‘“: 0.000032 ( 0 hom. )

Consequence

TNFAIP6
NM_007115.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.930
Variant links:
Genes affected
TNFAIP6 (HGNC:11898): (TNF alpha induced protein 6) The protein encoded by this gene is a secretory protein that contains a hyaluronan-binding domain, and thus is a member of the hyaluronan-binding protein family. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable complex with inter-alpha-inhibitor (I alpha I), and thus enhance the serine protease inhibitory activity of I alpha I, which is important in the protease network associated with inflammation. This gene can be induced by proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-1. Enhanced levels of this protein are found in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis.[provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.039523184).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNFAIP6NM_007115.4 linkuse as main transcriptc.402G>C p.Glu134Asp missense_variant 4/6 ENST00000243347.5
LOC101929319NR_110248.1 linkuse as main transcriptn.306+2768C>G intron_variant, non_coding_transcript_variant
TNFAIP6XM_047445635.1 linkuse as main transcriptc.402G>C p.Glu134Asp missense_variant 4/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNFAIP6ENST00000243347.5 linkuse as main transcriptc.402G>C p.Glu134Asp missense_variant 4/61 NM_007115.4 P1
TNFAIP6ENST00000460812.1 linkuse as main transcriptn.84G>C non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
AF:
0.000329
AC:
50
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000839
AC:
21
AN:
250186
Hom.:
0
AF XY:
0.0000666
AC XY:
9
AN XY:
135228
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1459380
Hom.:
0
Cov.:
30
AF XY:
0.0000317
AC XY:
23
AN XY:
725840
show subpopulations
Gnomad4 AFR exome
AF:
0.00123
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00116
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000793
Hom.:
0
Bravo
AF:
0.000325
ESP6500AA
AF:
0.00204
AC:
9
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 07, 2024The c.402G>C (p.E134D) alteration is located in exon 4 (coding exon 4) of the TNFAIP6 gene. This alteration results from a G to C substitution at nucleotide position 402, causing the glutamic acid (E) at amino acid position 134 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.085
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.52
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.69
N
REVEL
Benign
0.22
Sift
Benign
0.11
T
Sift4G
Benign
0.14
T
Polyphen
0.0010
B
Vest4
0.22
MutPred
0.52
Gain of catalytic residue at K133 (P = 0.1147);
MVP
0.35
MPC
0.23
ClinPred
0.023
T
GERP RS
-2.1
Varity_R
0.35
gMVP
0.62

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144393744; hg19: chr2-152226541; API