NM_001382548.1:c.639C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001382548.1(TCERG1):​c.639C>A​(p.Ala213Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,312,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TCERG1 NM_001382548.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-146459084-C-A is Benign according to our data. Variant chr5-146459084-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2655883.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>A	p.Ala213Ala	synonymous	Exon 4 of 23	NP_001369477.1	A0A7P0T8N8
	TCERG1	NM_006706.4		c.639C>A	p.Ala213Ala	synonymous	Exon 4 of 22	NP_006697.2
	TCERG1	NM_001400082.1		c.582C>A	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>A	p.Ala213Ala	synonymous	Exon 4 of 23	ENSP00000505217.1	A0A7P0T8N8
	TCERG1	ENST00000296702.9	TSL:1	c.639C>A	p.Ala213Ala	synonymous	Exon 4 of 22	ENSP00000296702.5	O14776-1
	TCERG1	ENST00000394421.7	TSL:1	c.639C>A	p.Ala213Ala	synonymous	Exon 4 of 21	ENSP00000377943.2	O14776-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1312018 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 654258

African (AFR) AF: 0.00 AC: 0 AN: 30428

American (AMR) AF: 0.00 AC: 0 AN: 41548

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 83284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44090

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

European-Non Finnish (NFE) AF: 0.00000202 AC: 2 AN: 989926

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.24
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;