X-102127041-A-G

Variant names:

• chrX-102127041-A-G
• NM_080390.4:c.211A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080390.4(TCEAL2):​c.211A>G​(p.Lys71Glu) 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. 14/20 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: TCEAL2 NM_080390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.226

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044582665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4	c.211A>G	p.Lys71Glu	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.211A>G	p.Lys71Glu	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1
TCEAL2	ENST00000329035.2	c.211A>G	p.Lys71Glu	missense_variant	Exon 3 of 3	5		ENSP00000332359.2
TCEAL2	ENST00000651085.1	n.153+596A>G		intron_variant	Intron 2 of 3
TCEAL2	ENST00000476749.1	n.*141A>G		downstream_gene_variant		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

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211A>G (p.K71E) alteration is located in exon 3 (coding exon 1) of the TCEAL2 gene. This alteration results from a A to G substitution at nucleotide position 211, causing the lysine (K) at amino acid position 71 to be replaced by a glutamic acid (E). 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	0.068
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	7.8
DANN	Benign	0.45
DEOGEN2	Benign	0.00065	T;T
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.30	T;.
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.49	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.019
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.15
MutPred		0.36		Loss of MoRF binding (P = 0.0019);Loss of MoRF binding (P = 0.0019);
MVP		0.082
MPC		0.38
ClinPred		0.024	T
GERP RS		-5.7
Varity_R		0.072
gMVP		0.022

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-101382013;