Genetic Variant NM_001382548.1:c.636G>T (chr5-146459081-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001382548.1(TCERG1):c.636G>T(p.Gln212His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000765 in 1,307,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q212R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

TCERG1
NM_001382548.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.637

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17855766).

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.636G>T	p.Gln212His	missense	Exon 4 of 23	NP_001369477.1	A0A7P0T8N8
TCERG1	NM_006706.4		c.636G>T	p.Gln212His	missense	Exon 4 of 22	NP_006697.2
TCERG1	NM_001400082.1		c.579G>T	p.Gln193His	missense	Exon 5 of 24	NP_001387011.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCERG1	ENST00000679501.2	MANE Select	c.636G>T	p.Gln212His	missense	Exon 4 of 23	ENSP00000505217.1	A0A7P0T8N8
TCERG1	ENST00000296702.9	TSL:1	c.636G>T	p.Gln212His	missense	Exon 4 of 22	ENSP00000296702.5	O14776-1
TCERG1	ENST00000394421.7	TSL:1	c.636G>T	p.Gln212His	missense	Exon 4 of 21	ENSP00000377943.2	O14776-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.65e-7

AC:

AN:

1307082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30340

American (AMR)

AF:

0.00

AC:

AN:

41474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24188

East Asian (EAS)

AF:

0.00

AC:

AN:

38814

South Asian (SAS)

AF:

0.00

AC:

AN:

83254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5076

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

985418

Other (OTH)

AF:

0.00

AC:

AN:

54448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.5

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.13

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.034

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.64

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.16

REVEL

Benign

0.13

Sift

Benign

0.077

Sift4G

Benign

0.18

Polyphen

0.94

Vest4

0.34

MutPred

0.45

Loss of solvent accessibility (P = 0.1651)

MVP

0.46

MPC

0.33

ClinPred

0.28

GERP RS

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.51

Mutation Taster

=99/1

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

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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