Genetic Variant NM_174937.4:c.1325C>T (chr10-131116869-G-A) – 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_174937.4(TCERG1L):c.1325C>T(p.Pro442Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000402 in 1,593,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TCERG1L
NM_174937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Publications

0 publications found

Variant links:

Genes affected

TCERG1L (HGNC:23533): (transcription elongation regulator 1 like) Predicted to enable RNA polymerase binding activity and transcription coregulator activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCERG1L links:

Genome browser will be placed here

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=0.08276874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174937.4. 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
	TCERG1L	NM_174937.4	MANE Select	c.1325C>T	p.Pro442Leu	missense	Exon 9 of 12	NP_777597.2	Q5VWI1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCERG1L	ENST00000368642.4	TSL:1 MANE Select	c.1325C>T	p.Pro442Leu	missense	Exon 9 of 12	ENSP00000357631.4	Q5VWI1
TCERG1L	ENST00000935680.1		c.1364C>T	p.Pro455Leu	missense	Exon 10 of 13	ENSP00000605739.1
TCERG1L	ENST00000483040.1	TSL:5	n.3187C>T		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000739

AC:

AN:

216574

AF XY:

0.0000944

show subpopulations

Gnomad AFR exome

AF:

0.000151

Gnomad AMR exome

AF:

0.0000974

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000519

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000382

AC:

AN:

1440804

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

714624

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33096

American (AMR)

AF:

0.000144

AC:

AN:

41556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25762

East Asian (EAS)

AF:

0.0000517

AC:

AN:

38696

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82722

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

51070

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000336

AC:

AN:

1102470

Other (OTH)

AF:

0.0000670

AC:

AN:

59680

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:

0.0000591

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41556

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000285

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000743

AC:

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

Benign

0.079

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.70

M_CAP

Benign

0.0043

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

3.3

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.024

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.016

Polyphen

0.70

Vest4

0.31

MVP

0.22

MPC

0.24

ClinPred

0.075

GERP RS

2.2

Varity_R

0.081

gMVP

0.46

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over