NM_015650.4:c.885G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015650.4(TRAF3IP1):​c.885G>T​(p.Lys295Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,409,052 control chromosomes in the GnomAD database, including 63,095 homozygotes. 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. K295K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.24 ( 5435 hom., cov: 31)
Exomes 𝑓: 0.30 ( 57660 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

3
15

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0600

Publications

25 publications found
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]
TRAF3IP1 Gene-Disease associations (from GenCC):
  • Senior-Loken syndrome 9
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • Senior-Loken syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • short rib-polydactyly syndrome, Majewski type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0013845861).
BP6
Variant 2-238329312-G-T is Benign according to our data. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-238329312-G-T is described in CliVar as Benign. Clinvar id is 1167550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRAF3IP1NM_015650.4 linkc.885G>T p.Lys295Asn missense_variant Exon 5 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.885G>T p.Lys295Asn missense_variant Exon 5 of 17 1 NM_015650.4 ENSP00000362424.4 Q8TDR0-1
TRAF3IP1ENST00000391993.7 linkc.885G>T p.Lys295Asn missense_variant Exon 5 of 15 1 ENSP00000375851.3 Q8TDR0-2
TRAF3IP1ENST00000409739.2 linkn.*754G>T non_coding_transcript_exon_variant Exon 5 of 5 3 ENSP00000386648.2 H7BZ10
TRAF3IP1ENST00000409739.2 linkn.*754G>T 3_prime_UTR_variant Exon 5 of 5 3 ENSP00000386648.2 H7BZ10

Frequencies

GnomAD3 genomes
AF:
0.243
AC:
36867
AN:
151992
Hom.:
5437
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0624
Gnomad AMI
AF:
0.280
Gnomad AMR
AF:
0.305
Gnomad ASJ
AF:
0.382
Gnomad EAS
AF:
0.230
Gnomad SAS
AF:
0.242
Gnomad FIN
AF:
0.276
Gnomad MID
AF:
0.446
Gnomad NFE
AF:
0.324
Gnomad OTH
AF:
0.284
GnomAD2 exomes
AF:
0.289
AC:
42716
AN:
147800
AF XY:
0.294
show subpopulations
Gnomad AFR exome
AF:
0.0587
Gnomad AMR exome
AF:
0.361
Gnomad ASJ exome
AF:
0.397
Gnomad EAS exome
AF:
0.235
Gnomad FIN exome
AF:
0.282
Gnomad NFE exome
AF:
0.327
Gnomad OTH exome
AF:
0.321
GnomAD4 exome
AF:
0.299
AC:
375680
AN:
1256942
Hom.:
57660
Cov.:
36
AF XY:
0.300
AC XY:
182204
AN XY:
607906
show subpopulations
African (AFR)
AF:
0.0530
AC:
1467
AN:
27686
American (AMR)
AF:
0.348
AC:
7826
AN:
22512
Ashkenazi Jewish (ASJ)
AF:
0.384
AC:
6668
AN:
17372
East Asian (EAS)
AF:
0.242
AC:
8507
AN:
35214
South Asian (SAS)
AF:
0.247
AC:
11113
AN:
45056
European-Finnish (FIN)
AF:
0.283
AC:
12859
AN:
45468
Middle Eastern (MID)
AF:
0.393
AC:
1942
AN:
4940
European-Non Finnish (NFE)
AF:
0.308
AC:
309894
AN:
1007474
Other (OTH)
AF:
0.301
AC:
15404
AN:
51220
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
14416
28831
43247
57662
72078
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10852
21704
32556
43408
54260
<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
AF:
0.242
AC:
36861
AN:
152110
Hom.:
5435
Cov.:
31
AF XY:
0.240
AC XY:
17869
AN XY:
74346
show subpopulations
African (AFR)
AF:
0.0623
AC:
2586
AN:
41532
American (AMR)
AF:
0.306
AC:
4662
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.382
AC:
1328
AN:
3472
East Asian (EAS)
AF:
0.230
AC:
1192
AN:
5174
South Asian (SAS)
AF:
0.242
AC:
1167
AN:
4822
European-Finnish (FIN)
AF:
0.276
AC:
2916
AN:
10568
Middle Eastern (MID)
AF:
0.432
AC:
127
AN:
294
European-Non Finnish (NFE)
AF:
0.324
AC:
22037
AN:
67966
Other (OTH)
AF:
0.280
AC:
591
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1349
2698
4046
5395
6744
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
394
788
1182
1576
1970
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.295
Hom.:
16662
Bravo
AF:
0.237
TwinsUK
AF:
0.301
AC:
1115
ALSPAC
AF:
0.302
AC:
1164
ESP6500AA
AF:
0.0670
AC:
295
ESP6500EA
AF:
0.320
AC:
2745
ExAC
AF:
0.281
AC:
32762
Asia WGS
AF:
0.258
AC:
900
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
May 22, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.73
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.014
.;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.32
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.75
T;T
MetaRNN
Benign
0.0014
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.4
M;M
PhyloP100
0.060
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.14
Sift
Benign
0.11
T;D
Sift4G
Benign
0.38
T;T
Polyphen
0.90
P;B
Vest4
0.16
MutPred
0.36
Loss of ubiquitination at K295 (P = 0.013);Loss of ubiquitination at K295 (P = 0.013);
MPC
0.21
ClinPred
0.018
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.10
gMVP
0.094
Mutation Taster
=96/4
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs12464423; hg19: chr2-239237953; COSMIC: COSV64852275; API