5-146459281-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_001382548.1(TCERG1):c.836C>T(p.Pro279Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,258 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 20 hom. )

Consequence

TCERG1
NM_001382548.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, TCERG1

BP4

Computational evidence support a benign effect (MetaRNN=0.004166484).

BP6

Variant 5-146459281-C-T is Benign according to our data. Variant chr5-146459281-C-T is described in ClinVar as [Benign]. Clinvar id is 714282.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0073 (1112/152370) while in subpopulation AFR AF= 0.0251 (1045/41588). AF 95% confidence interval is 0.0239. There are 5 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 1111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCERG1	NM_001382548.1 linkuse as main transcript	c.836C>T	p.Pro279Leu	missense_variant	4/23	ENST00000679501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCERG1	ENST00000679501.2 linkuse as main transcript	c.836C>T	p.Pro279Leu	missense_variant	4/23		NM_001382548.1	A2

Frequencies

GnomAD3 genomes

AF:

0.00730

AC:

1111

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00196

AC:

492

AN:

251454

Hom.:

AF XY:

0.00135

AC XY:

183

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0259

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000793

AC:

1160

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000652

AC XY:

474

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0278

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00730

AC:

1112

AN:

152370

Hom.:

Cov.:

AF XY:

0.00711

AC XY:

530

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000968

Hom.:

Bravo

AF:

0.00833

ESP6500AA

AF:

0.0252

AC:

111

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.068

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.041

Sift

Benign

0.33

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.0020

B;B

Vest4

0.41

MVP

0.22

MPC

0.36

ClinPred

0.014

GERP RS

4.4

Varity_R

0.062

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over