Variant 10-131104343-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174937.4(TCERG1L):c.1407T>A(p.Phe469Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000532 in 1,542,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

TCERG1L
NM_174937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCERG1L	NM_174937.4 linkuse as main transcript	c.1407T>A	p.Phe469Leu	missense_variant	10/12	ENST00000368642.4
TCERG1L	XM_047424966.1 linkuse as main transcript	c.1446T>A	p.Phe482Leu	missense_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCERG1L	ENST00000368642.4 linkuse as main transcript	c.1407T>A	p.Phe469Leu	missense_variant	10/12	1	NM_174937.4	P1
TCERG1L	ENST00000483040.1 linkuse as main transcript	n.3269T>A		non_coding_transcript_exon_variant	10/12	5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

158806

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

83486

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000599

Gnomad NFE exome

AF:

0.0000976

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000532

AC:

AN:

1390526

Hom.:

Cov.:

AF XY:

0.0000670

AC XY:

AN XY:

686574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000814

Gnomad4 NFE exome

AF:

0.0000626

Gnomad4 OTH exome

AF:

0.0000520

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000264

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

Mar 24, 2023

The c.1407T>A (p.F469L) alteration is located in exon 10 (coding exon 10) of the TCERG1L gene. This alteration results from a T to A substitution at nucleotide position 1407, causing the phenylalanine (F) at amino acid position 469 to be replaced by a leucine (L). 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

Pathogenic

1.0

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.25

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.28

Sift

Uncertain

0.025

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.73

MutPred

0.47

Gain of relative solvent accessibility (P = 0.005);

MVP

0.61

MPC

0.57

ClinPred

0.92

GERP RS

2.4

Varity_R

0.45

gMVP

0.71

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