Genetic Variant NM_001382548.1:c.275C>T (chr5-146455271-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001382548.1(TCERG1):c.275C>T(p.Pro92Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TCERG1
NM_001382548.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCERG1	NM_001382548.1	MANE Select	c.275C>T	p.Pro92Leu	missense	Exon 2 of 23	NP_001369477.1	A0A7P0T8N8
TCERG1	NM_006706.4		c.275C>T	p.Pro92Leu	missense	Exon 2 of 22	NP_006697.2
TCERG1	NM_001400082.1		c.218C>T	p.Pro73Leu	missense	Exon 3 of 24	NP_001387011.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCERG1	ENST00000679501.2	MANE Select	c.275C>T	p.Pro92Leu	missense	Exon 2 of 23	ENSP00000505217.1	A0A7P0T8N8
TCERG1	ENST00000296702.9	TSL:1	c.275C>T	p.Pro92Leu	missense	Exon 2 of 22	ENSP00000296702.5	O14776-1
TCERG1	ENST00000394421.7	TSL:1	c.275C>T	p.Pro92Leu	missense	Exon 2 of 21	ENSP00000377943.2	O14776-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251374

AF XY:

0.00000736

show subpopulations

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

7.3

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.20

Sift

Benign

0.32

Sift4G

Uncertain

0.0070

Polyphen

0.90

Vest4

0.66

MutPred

0.36

Loss of catalytic residue at P91 (P = 0.0194)

MVP

0.26

MPC

0.88

ClinPred

0.99

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.20

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over