Variant X-103274468-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001012979.3(TCEAL5):c.96T>A(p.Asp32Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,207,632 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 12 hem. )

Consequence

TCEAL5
NM_001012979.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.77

Variant links:

Genes affected

TCEAL5 (HGNC:22282): (transcription elongation factor A like 5) This gene, which is located on the X chromosome, encodes a protein which contains a BEX (brain expressed X-liked like family) domain. This domain is found in proteins encoded by the TCEAL elongation factor (transcription elongation factor A (SII)-like) gene family also located on the X chromosome. The coding region for this gene is located entirely in the terminal exon. [provided by RefSeq, Sep 2011]

TCEAL5 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=0.016112179).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL5	NM_001012979.3 linkuse as main transcript	c.96T>A	p.Asp32Glu	missense_variant	3/3	ENST00000372680.2	NP_001012997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL5	ENST00000372680.2 linkuse as main transcript	c.96T>A	p.Asp32Glu	missense_variant	3/3	1	NM_001012979.3	ENSP00000361765	P1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

109771

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

AN XY:

32247

show subpopulations

Gnomad AFR

AF:

0.000766

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000290

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000940

AC:

AN:

180907

Hom.:

AF XY:

0.0000908

AC XY:

AN XY:

66105

show subpopulations

Gnomad AFR exome

AF:

0.000999

Gnomad AMR exome

AF:

0.000147

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1097861

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363289

show subpopulations

Gnomad4 AFR exome

AF:

0.000758

Gnomad4 AMR exome

AF:

0.000142

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:

0.00

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000237

AC:

AN:

109771

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

AN XY:

32247

show subpopulations

Gnomad4 AFR

AF:

0.000766

Gnomad4 AMR

AF:

0.000290

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

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 23, 2023

The c.96T>A (p.D32E) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a T to A substitution at nucleotide position 96, causing the aspartic acid (D) at amino acid position 32 to be replaced by a glutamic acid (E). 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

0.083

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.16

DANN

Benign

0.34

DEOGEN2

Benign

0.0017

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.43

M_CAP

Benign

0.0025

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.76

REVEL

Benign

0.051

Sift

Benign

0.41

Sift4G

Benign

0.86

Polyphen

0.0040

Vest4

0.087

MutPred

0.37

Loss of ubiquitination at K35 (P = 0.0613);

MVP

0.12

MPC

0.60

ClinPred

0.0072

GERP RS

-2.5

Varity_R

0.052

gMVP

0.0041

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