3-185921116-C-CTA

Position:

• chr3-185921116-C-CTA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004593.3(TRA2B):​c.709_710insTA​(p.Ser237IlefsTer56) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRA2B NM_004593.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.53

Genes affected

TRA2B (HGNC:10781): (transformer 2 beta homolog) This gene encodes a nuclear protein which functions as sequence-specific serine/arginine splicing factor which plays a role in mRNA processing, splicing patterns, and gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRA2B	NM_004593.3	c.709_710insTA	p.Ser237IlefsTer56	frameshift_variant	6/9	ENST00000453386.7	NP_004584.1
TRA2B	NM_001243879.2	c.409_410insTA	p.Ser137IlefsTer56	frameshift_variant	5/8		NP_001230808.1
TRA2B	XM_047448717.1	c.409_410insTA	p.Ser137IlefsTer56	frameshift_variant	6/9		XP_047304673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRA2B	ENST00000453386.7	c.709_710insTA	p.Ser237IlefsTer56	frameshift_variant	6/9	1	NM_004593.3	ENSP00000416959	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2023

Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in abnormal protein length as the last 52 amino acids are replaced with 55 different amino acids in a gene for which loss-of-function is not an established mechanism of disease -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-185638904;