X-103274530-G-A

Variant summary

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

The NM_001012979.3(TCEAL5):​c.34C>T​(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,199,574 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.0000092 ( 0 hom. 0 hem. )

Consequence

TCEAL5
NM_001012979.3 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10
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=0.09160879).
BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCEAL5NM_001012979.3 linkc.34C>T p.Pro12Ser 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.34C>T p.Pro12Ser missense_variant Exon 3 of 3 1 NM_001012979.3 ENSP00000361765.1 Q5H9L2

Frequencies

GnomAD3 genomes
AF:
0.0000630
AC:
7
AN:
111057
Hom.:
0
Cov.:
22
AF XY:
0.0000600
AC XY:
2
AN XY:
33353
show subpopulations
Gnomad AFR
AF:
0.000164
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000954
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:
0.0000189
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000352
AC:
6
AN:
170558
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
58206
show subpopulations
Gnomad AFR exome
AF:
0.000463
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000919
AC:
10
AN:
1088517
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
356603
show subpopulations
Gnomad4 AFR exome
AF:
0.000351
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:
0.00
Gnomad4 OTH exome
AF:
0.0000219
GnomAD4 genome
AF:
0.0000630
AC:
7
AN:
111057
Hom.:
0
Cov.:
22
AF XY:
0.0000600
AC XY:
2
AN XY:
33353
show subpopulations
Gnomad4 AFR
AF:
0.000164
Gnomad4 AMR
AF:
0.0000954
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000189
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000151
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.34C>T (p.P12S) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a C to T substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 to be replaced by a serine (S). 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
0.13
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.091
T
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.13
Sift
Uncertain
0.021
D
Sift4G
Benign
0.45
T
Polyphen
0.98
D
Vest4
0.12
MVP
0.33
MPC
0.67
ClinPred
0.15
T
GERP RS
3.3
Varity_R
0.22
gMVP
0.021

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: rs141706642; hg19: chrX-102529458; API