NM_005879.3:c.*144G>T

Variant names:

• chr3-49828959-C-A
• rs1128535
• NM_005879.3:c.*144G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005879.3(TRAIP):​c.*144G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAIP NM_005879.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 38 publications found

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 Gene-Disease associations (from GenCC):

• Seckel syndrome 9

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAIP	NM_005879.3	c.*144G>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000331456.7	NP_005870.2
TRAIP	XM_017005526.2	c.*144G>T		3_prime_UTR_variant	Exon 12 of 12		XP_016861015.1
TRAIP	XM_047447240.1	c.*144G>T		3_prime_UTR_variant	Exon 10 of 10		XP_047303196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAIP	ENST00000331456.7	c.*144G>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_005879.3	ENSP00000328203.2
TRAIP	ENST00000491060.1	n.708G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
TRAIP	ENST00000473195.5	n.*727G>T		downstream_gene_variant		3		ENSP00000419556.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 998950 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 506694

African (AFR) AF: 0.00 AC: 0 AN: 24490

American (AMR) AF: 0.00 AC: 0 AN: 39002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19298

East Asian (EAS) AF: 0.00 AC: 0 AN: 36834

South Asian (SAS) AF: 0.00 AC: 0 AN: 68350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 722546

Other (OTH) AF: 0.00 AC: 0 AN: 44340

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.68
DANN	Benign	0.41
PhyloP100		-0.28

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

Other links and lift over

dbSNP: rs1128535; hg19: chr3-49866392;