NM_001382548.1:c.621T>G

Variant names:

• chr5-146459066-T-G
• rs183780634
• NM_001382548.1:c.621T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001382548.1(TCERG1):​c.621T>G​(p.Ala207Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,432,674 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 (★). Synonymous variant affecting the same amino acid position (i.e. A207A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: TCERG1 NM_001382548.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.51
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.11).
• BP6: Variant 5-146459066-T-G is Benign according to our data. Variant chr5-146459066-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2655880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.51 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.621T>G	p.Ala207Ala	synonymous	Exon 4 of 23	NP_001369477.1	A0A7P0T8N8
	TCERG1	NM_006706.4		c.621T>G	p.Ala207Ala	synonymous	Exon 4 of 22	NP_006697.2
	TCERG1	NM_001400082.1		c.564T>G	p.Ala188Ala	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.621T>G	p.Ala207Ala	synonymous	Exon 4 of 23	ENSP00000505217.1	A0A7P0T8N8
	TCERG1	ENST00000296702.9	TSL:1	c.621T>G	p.Ala207Ala	synonymous	Exon 4 of 22	ENSP00000296702.5	O14776-1
	TCERG1	ENST00000394421.7	TSL:1	c.621T>G	p.Ala207Ala	synonymous	Exon 4 of 21	ENSP00000377943.2	O14776-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000489 AC: 7 AN: 1432674 Hom.: 0 Cov.: 34 AF XY: 0.00000421 AC XY: 3 AN XY: 712500

African (AFR) AF: 0.00 AC: 0 AN: 32768

American (AMR) AF: 0.00 AC: 0 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.00 AC: 0 AN: 85286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51064

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5612

European-Non Finnish (NFE) AF: 0.00000551 AC: 6 AN: 1089902

Other (OTH) AF: 0.00 AC: 0 AN: 59130

GnomAD4 genome Cov.: 33

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	-1.1
CADD	Benign	0.0030
DANN	Benign	0.11
PhyloP100		-8.5
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: rs183780634; hg19: chr5-145838629;