Genetic Variant TCEAL6:p.Glu51Lys (chrX-102141181-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001006938.3(TCEAL6):c.151G>A(p.Glu51Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,210,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

TCEAL6
NM_001006938.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.858

Variant links:

Genes affected

TCEAL6 (HGNC:24553): (transcription elongation factor A like 6) Predicted to enable WW domain binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCEAL6 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=0.06710866).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL6	NM_001006938.3 link	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 3		NP_001006939.2	A0A024RCH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL6	ENST00000372774.8 link	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 4	1		ENSP00000361860.4		Q6IPX3
TCEAL6	ENST00000372773.2 link	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 4	3		ENSP00000361859.2		Q6IPX3

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112383

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34525

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000934

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

183491

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

67927

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1098266

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00000356

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112383

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34525

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000934

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151G>A (p.E51K) alteration is located in exon 3 (coding exon 1) of the TCEAL6 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glutamic acid (E) at amino acid position 51 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

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.066

DANN

Benign

0.53

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.47

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.61

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.0060

Sift

Benign

0.31

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0010

B;B

Vest4

0.14

MutPred

0.47

Gain of glycosylation at E51 (P = 0.0144);Gain of glycosylation at E51 (P = 0.0144);

MVP

0.068

MPC

0.20

ClinPred

0.026

GERP RS

-2.7

gMVP

0.024

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