rs864622784

chr3-49856402-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_005879.3(TRAIP):c.52C>T(p.Arg18Cys) 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). Synonymous variant affecting the same amino acid position (i.e. R18R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAIP NM_005879.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.23

Genes affected

TRAIP (HGNC:30764): (TRAF interacting protein) This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-associated factor 1 (TRAF1), TNFR-associated factor 2 (TRAF2), and cylindromatosis. The interaction with TRAF2 inhibits TRAF2-mediated nuclear factor kappa-B, subunit 1 activation that is required for cell activation and protection against apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-49856402-G-A is Pathogenic according to our data. Variant chr3-49856402-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 221233.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAIP	NM_005879.3	c.52C>T	p.Arg18Cys	missense_variant	1/15	ENST00000331456.7
TRAIP	XM_017005526.2	c.52C>T	p.Arg18Cys	missense_variant	1/12
TRAIP	XR_007094382.1	n.163C>T		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAIP	ENST00000331456.7	c.52C>T	p.Arg18Cys	missense_variant	1/15	1	NM_005879.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Seckel syndrome 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.28	T;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;.;.
Polyphen		1.0	D;.;.;.
Vest4		0.68
MutPred		0.50		Gain of catalytic residue at V20 (P = 0.0837);Gain of catalytic residue at V20 (P = 0.0837);Gain of catalytic residue at V20 (P = 0.0837);Gain of catalytic residue at V20 (P = 0.0837);
MVP		0.67
MPC		1.3
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.46
gMVP		0.61

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: rs864622784; hg19: chr3-49893835;