rs1697476086

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015650.4(TRAF3IP1):​c.8C>A​(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000403 in 1,241,124 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. 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. A3G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.395
Variant links:
Genes affected
TRAF3IP1 (HGNC:17861): (TRAF3 interacting protein 1) The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9. [provided by RefSeq, Mar 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07493213).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRAF3IP1NM_015650.4 linkc.8C>A p.Ala3Glu missense_variant Exon 1 of 17 ENST00000373327.5 NP_056465.2 Q8TDR0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRAF3IP1ENST00000373327.5 linkc.8C>A p.Ala3Glu missense_variant Exon 1 of 17 1 NM_015650.4 ENSP00000362424.4 Q8TDR0-1
TRAF3IP1ENST00000391993.7 linkc.8C>A p.Ala3Glu missense_variant Exon 1 of 15 1 ENSP00000375851.3 Q8TDR0-2
TRAF3IP1ENST00000409739.2 linkn.8C>A non_coding_transcript_exon_variant Exon 1 of 5 3 ENSP00000386648.2 H7BZ10

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000403
AC:
5
AN:
1241124
Hom.:
0
Cov.:
30
AF XY:
0.00000164
AC XY:
1
AN XY:
611382
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000506
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0057
.;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.64
T;T
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.075
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.075
N;N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.13
N;N
REVEL
Benign
0.022
Sift
Benign
0.29
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.0010
B;B
Vest4
0.12
MutPred
0.36
Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP
0.16
MPC
0.16
ClinPred
0.25
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.14
gMVP
0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-239229311; API