rs776946849

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_015650.4(TRAF3IP1):​c.1085C>G​(p.Ser362*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

TRAF3IP1
NM_015650.4 stop_gained

Scores

3
2
2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.00
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 Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRAF3IP1NM_015650.4 linkuse as main transcriptc.1085C>G p.Ser362* stop_gained 8/17 ENST00000373327.5 NP_056465.2 Q8TDR0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRAF3IP1ENST00000373327.5 linkuse as main transcriptc.1085C>G p.Ser362* stop_gained 8/171 NM_015650.4 ENSP00000362424.4 Q8TDR0-1
TRAF3IP1ENST00000391993.7 linkuse as main transcriptc.1063+4348C>G intron_variant 1 ENSP00000375851.3 Q8TDR0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, no assertion criteria providedresearchGharavi Laboratory, Columbia UniversitySep 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
37
DANN
Uncertain
1.0
Eigen
Pathogenic
0.74
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Benign
0.71
D
Vest4
0.096
GERP RS
2.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.30
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.30
Position offset: -21

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: rs776946849; hg19: chr2-239247024; API