Genetic Variant NM_015650.4:c.52C>G (chr2-238320714-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.52C>G(p.Arg18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,295,444 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. R18W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

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=0.23573157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 link	c.52C>G	p.Arg18Gly	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.52C>G	p.Arg18Gly	missense_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7 link	c.52C>G	p.Arg18Gly	missense_variant	Exon 1 of 15	1		ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000409739.2 link	n.52C>G		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2	H7BZ10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000232

AC:

AN:

1295444

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

639178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26104

American (AMR)

AF:

0.00

AC:

AN:

26874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21708

East Asian (EAS)

AF:

0.00

AC:

AN:

26688

South Asian (SAS)

AF:

0.00

AC:

AN:

71170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5048

European-Non Finnish (NFE)

AF:

0.00000294

AC:

AN:

1020884

Other (OTH)

AF:

0.00

AC:

AN:

51650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PhyloP100

2.2

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.067

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.72

P;P

Vest4

0.33

MutPred

0.33

Loss of MoRF binding (P = 0.0158);Loss of MoRF binding (P = 0.0158);

MVP

0.30

MPC

0.29

ClinPred

0.98

GERP RS

1.1

PromoterAI

0.043

Neutral

(source)

Varity_R

0.44

gMVP

0.31

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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NM_015650.4:c.52C>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