X-103587114-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001006935.3(TCEAL4):​c.439G>A​(p.Asp147Asn) 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 1,209,386 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.000045 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

TCEAL4
NM_001006935.3 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14748257).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCEAL4NM_001006935.3 linkc.439G>A p.Asp147Asn 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
TCEAL4ENST00000472484.6 linkc.439G>A p.Asp147Asn missense_variant Exon 3 of 3 1 NM_001006935.3 ENSP00000421156.1 Q96EI5-1

Frequencies

GnomAD3 genomes
AF:
0.0000448
AC:
5
AN:
111704
Hom.:
0
Cov.:
23
AF XY:
0.0000295
AC XY:
1
AN XY:
33870
show subpopulations
Gnomad AFR
AF:
0.000131
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000947
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000550
AC:
1
AN:
181871
Hom.:
0
AF XY:
0.0000150
AC XY:
1
AN XY:
66615
show subpopulations
Gnomad AFR exome
AF:
0.0000769
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:
0.00000273
AC:
3
AN:
1097682
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
363138
show subpopulations
Gnomad4 AFR exome
AF:
0.000114
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:
0.00
GnomAD4 genome
AF:
0.0000448
AC:
5
AN:
111704
Hom.:
0
Cov.:
23
AF XY:
0.0000295
AC XY:
1
AN XY:
33870
show subpopulations
Gnomad4 AFR
AF:
0.000131
Gnomad4 AMR
AF:
0.0000947
Gnomad4 ASJ
AF:
0.00
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
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.439G>A (p.D147N) 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 439, causing the aspartic acid (D) at amino acid position 147 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
0.26
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
.;T;T;T;T;T;T
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.73
T;.;.;.;T;.;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.15
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
.;M;M;M;.;M;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.5
D;D;D;D;.;D;D
REVEL
Benign
0.063
Sift
Uncertain
0.0030
D;D;D;D;.;D;D
Sift4G
Benign
0.12
T;T;T;T;T;T;T
Polyphen
1.0
.;D;D;D;.;D;D
Vest4
0.27
MutPred
0.50
.;Gain of MoRF binding (P = 0.0948);Gain of MoRF binding (P = 0.0948);Gain of MoRF binding (P = 0.0948);.;Gain of MoRF binding (P = 0.0948);Gain of MoRF binding (P = 0.0948);
MVP
0.39
MPC
0.62
ClinPred
0.48
T
GERP RS
3.1
Varity_R
0.25
gMVP
0.029

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: rs758997247; hg19: chrX-102842042; API