Genetic Variant TRAF3IP1:p.Ala3Gly (chr2-238320670-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015650.4(TRAF3IP1):c.8C>G(p.Ala3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,241,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.395

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):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Senior-Loken syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0752238).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015650.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP1	NM_015650.4	MANE Select	c.8C>G	p.Ala3Gly	missense	Exon 1 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.8C>G	p.Ala3Gly	missense	Exon 1 of 15	NP_001132962.1	Q8TDR0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAF3IP1	ENST00000373327.5	TSL:1 MANE Select	c.8C>G	p.Ala3Gly	missense	Exon 1 of 17	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7	TSL:1	c.8C>G	p.Ala3Gly	missense	Exon 1 of 15	ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000935943.1		c.8C>G	p.Ala3Gly	missense	Exon 1 of 16	ENSP00000606002.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000242

AC:

AN:

1241124

Hom.:

Cov.:

AF XY:

0.00000491

AC XY:

AN XY:

611382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25034

American (AMR)

AF:

0.00

AC:

AN:

23830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19926

East Asian (EAS)

AF:

0.00

AC:

AN:

24380

South Asian (SAS)

AF:

0.00

AC:

AN:

64112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4338

European-Non Finnish (NFE)

AF:

0.00000202

AC:

AN:

988984

Other (OTH)

AF:

0.0000207

AC:

AN:

48298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.68

M_CAP

Benign

0.057

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.44

PhyloP100

0.40

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.0

REVEL

Benign

0.027

Sift

Benign

0.34

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.063

MutPred

0.27

Loss of sheet (P = 0.0817)

MVP

0.23

MPC

0.14

ClinPred

0.17

GERP RS

2.4

PromoterAI

-0.022

Neutral

(source)

Varity_R

0.099

gMVP

0.22

Mutation Taster

=86/14

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over