2-238320690-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015650.4(TRAF3IP1):c.28C>G(p.Gln10Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000662 in 151,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Publications

0 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

TRAF3IP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 link	c.28C>G	p.Gln10Glu	missense_variant	Exon 1 of 17	ENST00000373327.5	NP_056465.2	Q8TDR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAF3IP1	ENST00000373327.5 link	c.28C>G	p.Gln10Glu	missense_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7 link	c.28C>G	p.Gln10Glu	missense_variant	Exon 1 of 15	1		ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000409739.2 link	n.28C>G		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2	H7BZ10

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1269226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

625956

African (AFR)

AF:

0.00

AC:

AN:

25598

American (AMR)

AF:

0.00

AC:

AN:

25278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20870

East Asian (EAS)

AF:

0.00

AC:

AN:

25468

South Asian (SAS)

AF:

0.00

AC:

AN:

67980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4780

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1005394

Other (OTH)

AF:

0.00

AC:

AN:

49966

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41348

American (AMR)

AF:

0.00

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67636

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.28C>G (p.Q10E) alteration is located in exon 1 (coding exon 1) of the TRAF3IP1 gene. This alteration results from a C to G substitution at nucleotide position 28, causing the glutamine (Q) at amino acid position 10 to be replaced by a glutamic acid (E). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.1

M;M

PhyloP100

6.3

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.067

T;T

Polyphen

0.78

P;P

Vest4

0.52

MutPred

0.46

Gain of disorder (P = 0.0546);Gain of disorder (P = 0.0546);

MVP

0.44

MPC

0.16

ClinPred

0.97

GERP RS

3.4

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.61

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-238320690-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over