5-146455186-CG-C

Variant names:

• chr5-146455186-CG-C
• rs1762720125
• NM_001382548.1:c.192delG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001382548.1(TCERG1):​c.192delG​(p.Pro65ArgfsTer40) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCERG1 NM_001382548.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.24
• Publications: 0 publications found

Genes affected

TCERG1 (HGNC:15630): (transcription elongation regulator 1) This gene encodes a nuclear protein that regulates transcriptional elongation and pre-mRNA splicing. The encoded protein interacts with the hyperphosphorylated C-terminal domain of RNA polymerase II via multiple FF domains, and with the pre-mRNA splicing factor SF1 via a WW domain. Alternative splicing results in multiple transcripts variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-146455186-CG-C is Pathogenic according to our data. Variant chr5-146455186-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 998159.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382548.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCERG1	NM_001382548.1	MANE Select	c.192delG	p.Pro65ArgfsTer40	frameshift	Exon 2 of 23	NP_001369477.1	A0A7P0T8N8
	TCERG1	NM_006706.4		c.192delG	p.Pro65ArgfsTer40	frameshift	Exon 2 of 22	NP_006697.2
	TCERG1	NM_001400082.1		c.135delG	p.Pro46ArgfsTer40	frameshift	Exon 3 of 24	NP_001387011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCERG1	ENST00000679501.2	MANE Select	c.192delG	p.Pro65ArgfsTer40	frameshift	Exon 2 of 23	ENSP00000505217.1	A0A7P0T8N8
	TCERG1	ENST00000296702.9	TSL:1	c.192delG	p.Pro65ArgfsTer40	frameshift	Exon 2 of 22	ENSP00000296702.5	O14776-1
	TCERG1	ENST00000394421.7	TSL:1	c.192delG	p.Pro65ArgfsTer40	frameshift	Exon 2 of 21	ENSP00000377943.2	O14776-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Colorectal cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

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: rs1762720125; hg19: chr5-145834749;