5-146447396-C-G

Position:

• chr5-146447396-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001382548.1(TCERG1):​c.47C>G​(p.Pro16Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCERG1 NM_001382548.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

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]

TCERG1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37032545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCERG1	NM_001382548.1	c.47C>G	p.Pro16Arg	missense_variant	1/23	ENST00000679501.2	NP_001369477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCERG1	ENST00000679501.2	c.47C>G	p.Pro16Arg	missense_variant	1/23		NM_001382548.1	ENSP00000505217.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.47C>G (p.P16R) alteration is located in exon 1 (coding exon 1) of the TCERG1 gene. This alteration results from a C to G substitution at nucleotide position 47, causing the proline (P) at amino acid position 16 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.097
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.57	T;T
Polyphen		0.54	P;P
Vest4		0.71
MutPred		0.28		Gain of MoRF binding (P = 0.0014);Gain of MoRF binding (P = 0.0014);
MVP		0.43
MPC		0.37
ClinPred		0.72	D
GERP RS		5.0
Varity_R		0.47
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-145826959;