X-103274029-A-G

Variant summary

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

The NM_001012979.3(TCEAL5):​c.535T>C​(p.Phe179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,210,039 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000015 ( 0 hom. 8 hem. )

Consequence

TCEAL5
NM_001012979.3 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07
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]

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=0.088474214).
BS2
High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCEAL5NM_001012979.3 linkc.535T>C p.Phe179Leu missense_variant Exon 3 of 3 ENST00000372680.2 NP_001012997.1 Q5H9L2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCEAL5ENST00000372680.2 linkc.535T>C p.Phe179Leu missense_variant Exon 3 of 3 1 NM_001012979.3 ENSP00000361765.1 Q5H9L2

Frequencies

GnomAD3 genomes
AF:
0.0000358
AC:
4
AN:
111770
Hom.:
0
Cov.:
24
AF XY:
0.0000295
AC XY:
1
AN XY:
33944
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000753
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000272
AC:
5
AN:
183521
Hom.:
0
AF XY:
0.0000589
AC XY:
4
AN XY:
67949
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:
0.0000488
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000146
AC:
16
AN:
1098269
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
8
AN XY:
363623
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000178
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000358
AC:
4
AN:
111770
Hom.:
0
Cov.:
24
AF XY:
0.0000295
AC XY:
1
AN XY:
33944
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000753
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.535T>C (p.F179L) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a T to C substitution at nucleotide position 535, causing the phenylalanine (F) at amino acid position 179 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
Pathogenic
0.75
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
15
DANN
Benign
0.92
DEOGEN2
Benign
0.012
T
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.088
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.051
Sift
Benign
0.17
T
Sift4G
Benign
0.38
T
Polyphen
0.031
B
Vest4
0.17
MutPred
0.55
Gain of relative solvent accessibility (P = 0.0098);
MVP
0.16
MPC
0.73
ClinPred
0.053
T
GERP RS
1.3
Varity_R
0.12
gMVP
0.011

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.

Other links and lift over

dbSNP: rs759909483; hg19: chrX-102528957; API