Genetic Variant NM_015650.4:c.90C>T (chr2-238320752-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_015650.4(TRAF3IP1):c.90C>T(p.Pro30Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,289,302 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. Synonymous variant affecting the same amino acid position (i.e. P30P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.417

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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=0.417 with no splicing effect.

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.90C>T	p.Pro30Pro	synonymous	Exon 1 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.90C>T	p.Pro30Pro	synonymous	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.90C>T	p.Pro30Pro	synonymous	Exon 1 of 17	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7	TSL:1	c.90C>T	p.Pro30Pro	synonymous	Exon 1 of 15	ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000935943.1		c.90C>T	p.Pro30Pro	synonymous	Exon 1 of 16	ENSP00000606002.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

99066

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000310

AC:

AN:

1289302

Hom.:

Cov.:

AF XY:

0.00000314

AC XY:

AN XY:

636170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25908

American (AMR)

AF:

0.00

AC:

AN:

26444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21440

East Asian (EAS)

AF:

0.00

AC:

AN:

26272

South Asian (SAS)

AF:

0.0000141

AC:

AN:

70876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5140

European-Non Finnish (NFE)

AF:

0.00000295

AC:

AN:

1016894

Other (OTH)

AF:

0.00

AC:

AN:

51210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.42

PromoterAI

0.089

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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