chr3-49856402-G-A

Position:

• 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).

• 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]

TRAIP (HGNC:):

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	Protein	UniProt
TRAIP	NM_005879.3	c.52C>T	p.Arg18Cys	missense_variant	1/15	ENST00000331456.7	NP_005870.2
TRAIP	XM_017005526.2	c.52C>T	p.Arg18Cys	missense_variant	1/12		XP_016861015.1
TRAIP	XR_007094382.1	n.163C>T		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAIP	ENST00000331456.7	c.52C>T	p.Arg18Cys	missense_variant	1/15	1	NM_005879.3	ENSP00000328203.2

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;.;.;.
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;