Genetic Variant TCEAL4:p.Ser102Asn (chrX-103586980-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_001006935.3(TCEAL4):c.305G>A(p.Ser102Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,208,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.000036 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

TCEAL4
NM_001006935.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.12

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.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity TCAL4_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.045969814).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL4	NM_001006935.3 link	c.305G>A	p.Ser102Asn	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.305G>A	p.Ser102Asn	missense_variant	Exon 3 of 3	1	NM_001006935.3	ENSP00000421156.1		Q96EI5-1

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110797

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

32983

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:

0.00114

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

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1098132

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000132

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110797

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

32983

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00114

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305G>A (p.S102N) alteration is located in exon 3 (coding exon 1) of the TCEAL4 gene. This alteration results from a G to A substitution at nucleotide position 305, causing the serine (S) at amino acid position 102 to be replaced by an asparagine (N). 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

0.082

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

DANN

Benign

0.85

DEOGEN2

Benign

0.087

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

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.53

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

M_CAP

Benign

0.0015

MetaRNN

Benign

0.046

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M;M;M;.;M;M;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N;N;N;.;N;N;N

REVEL

Benign

0.0040

Sift

Uncertain

0.0050

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

Sift4G

Uncertain

0.038

D;D;D;D;T;D;D;T

Polyphen

0.32

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

Vest4

0.13

MutPred

0.27

.;Loss of phosphorylation at S102 (P = 9e-04);Loss of phosphorylation at S102 (P = 9e-04);Loss of phosphorylation at S102 (P = 9e-04);.;Loss of phosphorylation at S102 (P = 9e-04);Loss of phosphorylation at S102 (P = 9e-04);Loss of phosphorylation at S102 (P = 9e-04);

MVP

0.082

MPC

0.85

ClinPred

0.20

GERP RS

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.99

Varity_R

0.14

gMVP

0.0077

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