GeneBe

chr2-238329333-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_015650.4(TRAF3IP1):​c.906T>G​(p.Pro302Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,357,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P302P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.68

Publications

5 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: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 2-238329333-T-G is Benign according to our data. Variant chr2-238329333-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2793156.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.68 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRAF3IP1NM_015650.4 linkc.906T>G p.Pro302Pro synonymous_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.906T>G p.Pro302Pro synonymous_variant Exon 5 of 17 1 NM_015650.4 ENSP00000362424.4 Q8TDR0-1
TRAF3IP1ENST00000391993.7 linkc.906T>G p.Pro302Pro synonymous_variant Exon 5 of 15 1 ENSP00000375851.3 Q8TDR0-2
TRAF3IP1ENST00000409739.2 linkn.*775T>G non_coding_transcript_exon_variant Exon 5 of 5 3 ENSP00000386648.2 H7BZ10
TRAF3IP1ENST00000409739.2 linkn.*775T>G 3_prime_UTR_variant Exon 5 of 5 3 ENSP00000386648.2 H7BZ10

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152028
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
8.29e-7
AC:
1
AN:
1205758
Hom.:
0
Cov.:
32
AF XY:
0.00000173
AC XY:
1
AN XY:
579364
show subpopulations
African (AFR)
AF:
0.0000385
AC:
1
AN:
25968
American (AMR)
AF:
0.00
AC:
0
AN:
20678
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16254
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32642
South Asian (SAS)
AF:
0.00
AC:
0
AN:
34468
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42964
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4754
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
979336
Other (OTH)
AF:
0.00
AC:
0
AN:
48694
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000658
AC:
1
AN:
152028
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74268
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41346
American (AMR)
AF:
0.00
AC:
0
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68012
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
116

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 29, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.040
DANN
Benign
0.18
PhyloP100
-2.7
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs17854985; hg19: chr2-239237974; API