rs747842883

Variant names:

• chrX-103253845-T-A
• rs747842883
• NM_153333.3:c.135A>T

Variant summary

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

The NM_153333.3(TCEAL8):​c.135A>T​(p.Glu45Asp) 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 NM_153333.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0540

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=0.20850998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL8	NM_153333.3	c.135A>T	p.Glu45Asp	missense_variant	Exon 3 of 3	ENST00000372685.8	NP_699164.1
TCEAL8	NM_001006684.2	c.135A>T	p.Glu45Asp	missense_variant	Exon 2 of 2		NP_001006685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL8	ENST00000372685.8	c.135A>T	p.Glu45Asp	missense_variant	Exon 3 of 3	1	NM_153333.3	ENSP00000361770.3
TCEAL8	ENST00000360000.8	c.135A>T	p.Glu45Asp	missense_variant	Exon 2 of 2	1		ENSP00000353093.4
TCEAL8	ENST00000451678.1	c.90+45A>T		intron_variant	Intron 3 of 3	3		ENSP00000390880.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.135A>T (p.E45D) alteration is located in exon 3 (coding exon 1) of the TCEAL8 gene. This alteration results from a A to T substitution at nucleotide position 135, causing the glutamic acid (E) at amino acid position 45 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;D
Vest4		0.16
MutPred		0.29		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.11
MPC		0.38
ClinPred		0.60	D
GERP RS		-0.51
BranchPoint Hunter		1.0
Varity_R		0.19
gMVP		0.21

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

Other links and lift over

dbSNP: rs747842883; hg19: chrX-102508773;