X-103253925-C-T

Position:

• chrX-103253925-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000372685.8(TCEAL8):​c.55G>A​(p.Glu19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
• Consequence: TCEAL8 ENST00000372685.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

Genes affected

TCEAL8 (HGNC:28683): (transcription elongation factor A like 8) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family contain TFA domains and may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.23971981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL8	NM_153333.3	c.55G>A	p.Glu19Lys	missense_variant	3/3	ENST00000372685.8	NP_699164.1
TCEAL8	NM_001006684.2	c.55G>A	p.Glu19Lys	missense_variant	2/2		NP_001006685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL8	ENST00000372685.8	c.55G>A	p.Glu19Lys	missense_variant	3/3	1	NM_153333.3	ENSP00000361770.3
TCEAL8	ENST00000360000.8	c.55G>A	p.Glu19Lys	missense_variant	2/2	1		ENSP00000353093.4
TCEAL8	ENST00000451678.1	c.55G>A	p.Glu19Lys	missense_variant	3/4	3		ENSP00000390880.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.55G>A (p.E19K) alteration is located in exon 3 (coding exon 1) of the TCEAL8 gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glutamic acid (E) at amino acid position 19 to be replaced by a lysine (K). 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	0.089
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T;T;T
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.070
Sift	Benign	0.066	T;T;D
Sift4G	Uncertain	0.032	D;D;.
Polyphen		0.99	D;D;.
Vest4		0.22
MutPred		0.44		Gain of ubiquitination at E19 (P = 0.0018);Gain of ubiquitination at E19 (P = 0.0018);Gain of ubiquitination at E19 (P = 0.0018);
MVP		0.030
MPC		1.2
ClinPred		0.94	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.20
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-102508853; COSMIC: COSV99056095; COSMIC: COSV99056095;