chrX-103586923-A-G

Variant names:

• chrX-103586923-A-G
• NM_001006935.3:c.248A>G

Variant summary

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

The NM_001006935.3(TCEAL4):​c.248A>G​(p.Glu83Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TCEAL4 NM_001006935.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.812

Genes affected

TCEAL4 (HGNC:26121): (transcription elongation factor A like 4) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. This family is comprised of nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternatively splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 13. [provided by RefSeq, Apr 2015]

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=0.09887627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL4	NM_001006935.3	c.248A>G	p.Glu83Gly	missense_variant	Exon 3 of 3	ENST00000472484.6	NP_001006936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL4	ENST00000472484.6	c.248A>G	p.Glu83Gly	missense_variant	Exon 3 of 3	1	NM_001006935.3	ENSP00000421156.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248A>G (p.E83G) alteration is located in exon 3 (coding exon 1) of the TCEAL4 gene. This alteration results from a A to G substitution at nucleotide position 248, causing the glutamic acid (E) at amino acid position 83 to be replaced by a glycine (G). 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	0.081
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.096	.;T;T;T;T;T;T;T
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.40	T;.;.;.;T;.;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.099	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	.;L;L;L;.;L;L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N;N;N;N;D;N;N;N
REVEL	Benign	0.020
Sift	Uncertain	0.0030	D;D;D;D;T;D;D;D
Sift4G	Benign	0.069	T;T;T;T;D;T;T;T
Polyphen		0.0010	.;B;B;B;.;B;B;.
Vest4		0.11
MutPred		0.39		.;Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);
MVP		0.043
MPC		1.2
ClinPred		0.31	T
GERP RS		0.93
Varity_R		0.084
gMVP		0.027

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-102841851;