Genetic Variant TCEAL4:p.Pro30Leu (chrX-103586764-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001006935.3(TCEAL4):c.89C>T(p.Pro30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,210,029 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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., 1 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 6 hem. )

Consequence

TCEAL4
NM_001006935.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.243

Variant links:

Genes affected

TCEAL4 (HGNC:26121): (transcription elongation factor A like 4) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. This family is comprised of nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternatively splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 13. [provided by RefSeq, Apr 2015]

TCEAL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07293698).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL4	NM_001006935.3 link	c.89C>T	p.Pro30Leu	missense_variant	Exon 3 of 3	ENST00000472484.6	NP_001006936.1	Q96EI5-1A0A384NKK0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL4	ENST00000472484.6 link	c.89C>T	p.Pro30Leu	missense_variant	Exon 3 of 3	1	NM_001006935.3	ENSP00000421156.1		Q96EI5-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112073

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34269

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000756

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:

0.0000386

AC:

AN:

181558

Hom.:

AF XY:

0.0000749

AC XY:

AN XY:

66792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000937

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:

0.0000146

AC:

AN:

1097956

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000619

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112073

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34269

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000756

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.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.89C>T (p.P30L) alteration is located in exon 3 (coding exon 1) of the TCEAL4 gene. This alteration results from a C to T substitution at nucleotide position 89, causing the proline (P) at amino acid position 30 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

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

.;T;T;T;T;.;T;T;T;.;T;T

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.71

T;.;.;.;T;T;T;.;T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.073

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.8

.;L;L;L;.;.;.;L;L;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.2

D;D;D;D;.;D;D;D;D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.079

T;T;T;T;.;T;T;T;T;T;T;T

Sift4G

Benign

0.068

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.11

.;B;B;B;.;.;.;B;B;.;.;.

Vest4

0.059

MutPred

0.56

.;Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);Loss of phosphorylation at T33 (P = 0.0711);

MVP

0.49

MPC

1.3

ClinPred

0.39

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.048

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