Genetic Variant NM_015650.4:c.22C>G (chr2-238320684-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.22C>G(p.Arg8Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000238 in 1,262,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R8W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.80

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20115569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 link	c.22C>G	p.Arg8Gly	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.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7 link	c.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 15	1		ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000409739.2 link	n.22C>G		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2	H7BZ10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000238

AC:

AN:

1262684

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

622666

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25470

American (AMR)

AF:

0.0000401

AC:

AN:

24964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20610

East Asian (EAS)

AF:

0.00

AC:

AN:

25154

South Asian (SAS)

AF:

0.00

AC:

AN:

67260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4606

European-Non Finnish (NFE)

AF:

0.00000200

AC:

AN:

1001474

Other (OTH)

AF:

0.00

AC:

AN:

49608

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

4.8

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.064

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.54

P;B

Vest4

0.26

MutPred

0.29

Loss of stability (P = 0.0248);Loss of stability (P = 0.0248);

MVP

0.30

MPC

0.29

ClinPred

0.99

GERP RS

3.4

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.51

gMVP

0.44

Mutation Taster

=38/62

disease causing

(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.

NM_015650.4:c.22C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over