X-103629944-G-C

Variant names:

• chrX-103629944-G-C
• NM_004780.3:c.28G>C

Variant summary

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

The NM_004780.3(TCEAL1):​c.28G>C​(p.Glu10Gln) 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. 10/17 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: TCEAL1 NM_004780.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

Genes affected

TCEAL1 (HGNC:11616): (transcription elongation factor A like 1) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. The encoded protein is similar to transcription elongation factor A/transcription factor SII and contains a zinc finger-like motif as well as a sequence related to the transcription factor SII Pol II-binding region. It may exert its effects via protein-protein interactions with other transcriptional regulators rather than via direct binding of DNA. 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=0.23077488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL1	NM_004780.3	c.28G>C	p.Glu10Gln	missense_variant	Exon 3 of 3	ENST00000372625.8	NP_004771.2
TCEAL1	NM_001006639.2	c.28G>C	p.Glu10Gln	missense_variant	Exon 3 of 3		NP_001006640.1
TCEAL1	NM_001006640.2	c.28G>C	p.Glu10Gln	missense_variant	Exon 3 of 3		NP_001006641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL1	ENST00000372625.8	c.28G>C	p.Glu10Gln	missense_variant	Exon 3 of 3	1	NM_004780.3	ENSP00000361708.3
TCEAL1	ENST00000372624.3	c.28G>C	p.Glu10Gln	missense_variant	Exon 3 of 3	1		ENSP00000361707.3
TCEAL1	ENST00000469820.1	n.493G>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
TCEAL1	ENST00000372626.7	c.28G>C	p.Glu10Gln	missense_variant	Exon 3 of 3	2		ENSP00000361709.3

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

Inborn genetic diseases Uncertain:1

Mar 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.28G>C (p.E10Q) alteration is located in exon 3 (coding exon 1) of the TCEAL1 gene. This alteration results from a G to C substitution at nucleotide position 28, causing the glutamic acid (E) at amino acid position 10 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
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.59	.;.;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.073
Sift	Uncertain	0.015	D;D;D
Sift4G	Benign	0.25	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.21
MutPred		0.41		Gain of ubiquitination at K6 (P = 0.1489);Gain of ubiquitination at K6 (P = 0.1489);Gain of ubiquitination at K6 (P = 0.1489);
MVP		0.18
MPC		1.9
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.26

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-102884872;