Variant X-103331459-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000332431.5(TCEAL7):c.56G>A(p.Arg19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000673 in 1,203,741 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000063 ( 0 hom. 24 hem. )

Consequence

TCEAL7
ENST00000332431.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.221

Variant links:

Genes affected

TCEAL7 (HGNC:28336): (transcription elongation factor A like 7) Predicted to enable WW domain binding activity. Involved in negative regulation of NF-kappaB transcription factor activity and negative regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TCEAL7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036284506).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL7	NM_152278.5 linkuse as main transcript	c.56G>A	p.Arg19Lys	missense_variant	3/3	ENST00000332431.5	NP_689491.1
TCEAL7	NM_001348258.2 linkuse as main transcript	c.56G>A	p.Arg19Lys	missense_variant	3/3		NP_001335187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL7	ENST00000332431.5 linkuse as main transcript	c.56G>A	p.Arg19Lys	missense_variant	3/3	1	NM_152278.5	ENSP00000329794	P1
TCEAL7	ENST00000372666.1 linkuse as main transcript	c.56G>A	p.Arg19Lys	missense_variant	3/3	2		ENSP00000361751	P1

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

111331

Hom.:

Cov.:

AF XY:

0.0000893

AC XY:

AN XY:

33593

show subpopulations

Gnomad AFR

AF:

0.0000327

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:

0.000207

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000426

AC:

AN:

164375

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54559

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:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000632

AC:

AN:

1092410

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

359186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

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:

0.00

Gnomad4 NFE exome

AF:

0.0000811

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000108

AC:

AN:

111331

Hom.:

Cov.:

AF XY:

0.0000893

AC XY:

AN XY:

33593

show subpopulations

Gnomad4 AFR

AF:

0.0000327

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:

0.000207

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000299

AC:

ExAC

AF:

0.0000166

AC:

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

Jan 26, 2023

The c.56G>A (p.R19K) alteration is located in exon 3 (coding exon 1) of the TCEAL7 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a lysine (K). 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

0.076

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.1

DANN

Benign

0.97

DEOGEN2

Benign

0.0081

T;T

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.48

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.076

Sift

Benign

1.0

T;T

Sift4G

Benign

0.84

T;T

Polyphen

0.17

B;B

Vest4

0.067

MVP

0.014

MPC

0.56

ClinPred

0.060

GERP RS

4.1

Varity_R

0.20

gMVP

0.24

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