chr2-238320713-T-G

Position:

• chr2-238320713-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM5 PP5

The NM_015650.4(TRAF3IP1):​c.51T>G​(p.Ile17Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I17S) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAF3IP1 NM_015650.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.228

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
• PP5: Variant 2-238320713-T-G is Pathogenic according to our data. Variant chr2-238320713-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 254150.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP1	NM_015650.4	c.51T>G	p.Ile17Met	missense_variant	1/17	ENST00000373327.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP1	ENST00000373327.5	c.51T>G	p.Ile17Met	missense_variant	1/17	1	NM_015650.4
TRAF3IP1	ENST00000391993.7	c.51T>G	p.Ile17Met	missense_variant	1/15	1		P1
TRAF3IP1	ENST00000409739.2	c.51T>G	p.Ile17Met	missense_variant, NMD_transcript_variant	1/5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Senior-Loken syndrome 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.65
MutPred		0.53		Gain of disorder (P = 0.0259);Gain of disorder (P = 0.0259);
MVP		0.25
MPC		0.33
ClinPred		0.96	D
GERP RS		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs886037899; hg19: chr2-239229354;