X-103609089-G-C

Variant names:

• chrX-103609089-G-C
• NM_032926.3:c.25G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032926.3(TCEAL3):​c.25G>C​(p.Glu9Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL3 NM_032926.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

Genes affected

TCEAL3 (HGNC:28247): (transcription elongation factor A like 3) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32206982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL3	NM_032926.3	c.25G>C	p.Glu9Gln	missense_variant	Exon 3 of 3	ENST00000372627.10	NP_116315.1
TCEAL3	NM_001006933.2	c.25G>C	p.Glu9Gln	missense_variant	Exon 3 of 3		NP_001006934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL3	ENST00000372627.10	c.25G>C	p.Glu9Gln	missense_variant	Exon 3 of 3	1	NM_032926.3	ENSP00000361710.5
TCEAL3	ENST00000243286.7	c.25G>C	p.Glu9Gln	missense_variant	Exon 3 of 3	1		ENSP00000243286.3
TCEAL3	ENST00000372628.5	c.25G>C	p.Glu9Gln	missense_variant	Exon 3 of 3	5		ENSP00000361711.1
TCEAL3	ENST00000477014.1	n.158+416G>C		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25G>C (p.E9Q) alteration is located in exon 3 (coding exon 1) of the TCEAL3 gene. This alteration results from a G to C substitution at nucleotide position 25, causing the glutamic acid (E) at amino acid position 9 to be replaced by a glutamine (Q). 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	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.51	.;T;.
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.038	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.15
MutPred		0.51		Gain of MoRF binding (P = 0.1123);Gain of MoRF binding (P = 0.1123);Gain of MoRF binding (P = 0.1123);
MVP		0.43
MPC		2.0
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.20
gMVP		0.025

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-102864017;