5-146459084-C-T

Variant names:

• chr5-146459084-C-T
• rs187468589
• NM_001382548.1:c.639C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001382548.1(TCERG1):​c.639C>T​(p.Ala213Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000731 in 136,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A213A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCERG1 NM_001382548.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.

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.639C>T	p.Ala213Ala	synonymous	Exon 4 of 23	NP_001369477.1	A0A7P0T8N8
	TCERG1	NM_006706.4		c.639C>T	p.Ala213Ala	synonymous	Exon 4 of 22	NP_006697.2
	TCERG1	NM_001400082.1		c.582C>T	p.Ala194Ala	synonymous	Exon 5 of 24	NP_001387011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCERG1	ENST00000679501.2	MANE Select	c.639C>T	p.Ala213Ala	synonymous	Exon 4 of 23	ENSP00000505217.1	A0A7P0T8N8
	TCERG1	ENST00000296702.9	TSL:1	c.639C>T	p.Ala213Ala	synonymous	Exon 4 of 22	ENSP00000296702.5	O14776-1
	TCERG1	ENST00000394421.7	TSL:1	c.639C>T	p.Ala213Ala	synonymous	Exon 4 of 21	ENSP00000377943.2	O14776-2

Frequencies

GnomAD3 genomes AF: 0.00000731 AC: 1 AN: 136774 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000171 AC: 4 AN: 233274 AF XY: 0.0000235

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000390

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000556 AC: 73 AN: 1311918 Hom.: 0 Cov.: 33 AF XY: 0.0000566 AC XY: 37 AN XY: 654204

African (AFR) AF: 0.0000329 AC: 1 AN: 30426

American (AMR) AF: 0.00 AC: 0 AN: 41546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24218

East Asian (EAS) AF: 0.00 AC: 0 AN: 38846

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5084

European-Non Finnish (NFE) AF: 0.0000717 AC: 71 AN: 989834

Other (OTH) AF: 0.00 AC: 0 AN: 54594

GnomAD4 genome AF: 0.00000731 AC: 1 AN: 136774 Hom.: 0 Cov.: 32 AF XY: 0.0000150 AC XY: 1 AN XY: 66756

African (AFR) AF: 0.00 AC: 0 AN: 37692

American (AMR) AF: 0.00 AC: 0 AN: 14048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3250

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4648

European-Finnish (FIN) AF: 0.000115 AC: 1 AN: 8682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60476

Other (OTH) AF: 0.00 AC: 0 AN: 1862

Alfa AF: 0.00102 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.0020
DANN	Benign	0.22
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs187468589; hg19: chr5-145838647; COSMIC: COSV57033698; COSMIC: COSV57033698;