X-102140952-T-A

Variant names:

• chrX-102140952-T-A
• ENST00000372774.8:c.380A>T

Variant summary

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

The NM_001006938.3(TCEAL6):​c.380A>T​(p.Glu127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL6 NM_001006938.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

Genes affected

TCEAL6 (HGNC:24553): (transcription elongation factor A like 6) Predicted to enable WW domain binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL6	NM_001006938.3	c.380A>T	p.Glu127Val	missense_variant	Exon 3 of 3		NP_001006939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL6	ENST00000372774.8	c.380A>T	p.Glu127Val	missense_variant	Exon 3 of 4	1		ENSP00000361860.4
TCEAL6	ENST00000372773.2	c.380A>T	p.Glu127Val	missense_variant	Exon 3 of 4	3		ENSP00000361859.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.380A>T (p.E127V) alteration is located in exon 3 (coding exon 1) of the TCEAL6 gene. This alteration results from a A to T substitution at nucleotide position 380, causing the glutamic acid (E) at amino acid position 127 to be replaced by a valine (V). 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	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.86	.;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.39
MutPred		0.62		Loss of methylation at K123 (P = 0.0919);Loss of methylation at K123 (P = 0.0919);
MVP		0.85
MPC		0.72
ClinPred		0.99	D
GERP RS		3.0
gMVP		0.073

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-101395924;