Variant chr10-131166826-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174937.4(TCERG1L):c.916A>C(p.Lys306Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

TCERG1L
NM_174937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06796253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCERG1L	NM_174937.4 link	c.916A>C	p.Lys306Gln	missense_variant	5/12	ENST00000368642.4	NP_777597.2	Q5VWI1
TCERG1L	XM_047424966.1 link	c.916A>C	p.Lys306Gln	missense_variant	5/13		XP_047280922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCERG1L	ENST00000368642.4 link	c.916A>C	p.Lys306Gln	missense_variant	5/12	1	NM_174937.4	ENSP00000357631.4		Q5VWI1
TCERG1L	ENST00000483040.1 link	n.138A>C		non_coding_transcript_exon_variant	2/12	5

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

250916

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000423

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000307

AC:

448

AN:

1461554

Hom.:

Cov.:

AF XY:

0.000304

AC XY:

221

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000177

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.916A>C (p.K306Q) alteration is located in exon 5 (coding exon 5) of the TCERG1L gene. This alteration results from a A to C substitution at nucleotide position 916, causing the lysine (K) at amino acid position 306 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.33

M_CAP

Benign

0.0044

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.3

REVEL

Benign

0.025

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.025

Polyphen

0.075

Vest4

0.18

MVP

0.35

MPC

0.16

ClinPred

0.063

GERP RS

2.4

Varity_R

0.21

gMVP

0.33

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