Genetic Variant TRAF3IP1:p.Ala3Glu (chr2-238320670-C-A) – 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>A(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000403 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.07493213).

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>A	p.Ala3Glu	missense	Exon 1 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.8C>A	p.Ala3Glu	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>A	p.Ala3Glu	missense	Exon 1 of 17	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7	TSL:1	c.8C>A	p.Ala3Glu	missense	Exon 1 of 15	ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000935943.1		c.8C>A	p.Ala3Glu	missense	Exon 1 of 16	ENSP00000606002.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000403

AC:

AN:

1241124

Hom.:

Cov.:

AF XY:

0.00000164

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:

0.00000506

AC:

AN:

988984

Other (OTH)

AF:

0.00

AC:

AN:

48298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.605

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.64

M_CAP

Benign

0.081

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.075

PhyloP100

0.40

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.13

REVEL

Benign

0.022

Sift

Benign

0.29

Sift4G

Benign

0.23

Polyphen

0.0010

Vest4

0.12

MutPred

0.36

Gain of helix (P = 0.0078)

MVP

0.16

MPC

0.16

ClinPred

0.25

GERP RS

2.4

PromoterAI

-0.0024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.14

gMVP

0.42

Mutation Taster

=89/11

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

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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