X-102126841-T-A

Variant names:

• chrX-102126841-T-A
• NM_080390.4:c.11T>A

Variant summary

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

The NM_080390.4(TCEAL2):​c.11T>A​(p.Leu4His) 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: 24)
• Consequence: TCEAL2 NM_080390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00500

Genes affected

TCEAL2 (HGNC:29818): (transcription elongation factor A like 2) 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. [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=0.114554316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4	c.11T>A	p.Leu4His	missense_variant	Exon 3 of 3	ENST00000372780.6	NP_525129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL2	ENST00000372780.6	c.11T>A	p.Leu4His	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1
TCEAL2	ENST00000476749.1	n.796T>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
TCEAL2	ENST00000329035.2	c.11T>A	p.Leu4His	missense_variant	Exon 3 of 3	5		ENSP00000332359.2
TCEAL2	ENST00000651085.1	n.153+396T>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11T>A (p.L4H) alteration is located in exon 3 (coding exon 1) of the TCEAL2 gene. This alteration results from a T to A substitution at nucleotide position 11, causing the leucine (L) at amino acid position 4 to be replaced by a histidine (H). 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	0.091
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.069	T;T
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.61	T;.
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.047
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.88	P;P
Vest4		0.27
MutPred		0.43		Loss of stability (P = 0.0073);Loss of stability (P = 0.0073);
MVP		0.068
MPC		0.12
ClinPred		0.55	D
GERP RS		-0.44
Varity_R		0.47
gMVP		0.092

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-101381813;