X-103273996-C-T

Variant names:

• chrX-103273996-C-T
• NM_001012979.3:c.568G>A

Variant summary

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

The NM_001012979.3(TCEAL5):​c.568G>A​(p.Val190Met) 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: 23)
• Consequence: TCEAL5 NM_001012979.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.681

Genes affected

TCEAL5 (HGNC:22282): (transcription elongation factor A like 5) This gene, which is located on the X chromosome, encodes a protein which contains a BEX (brain expressed X-liked like family) domain. This domain is found in proteins encoded by the TCEAL elongation factor (transcription elongation factor A (SII)-like) gene family also located on the X chromosome. The coding region for this gene is located entirely in the terminal exon. [provided by RefSeq, Sep 2011]

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=0.043262154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL5	NM_001012979.3	c.568G>A	p.Val190Met	missense_variant	Exon 3 of 3	ENST00000372680.2	NP_001012997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL5	ENST00000372680.2	c.568G>A	p.Val190Met	missense_variant	Exon 3 of 3	1	NM_001012979.3	ENSP00000361765.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.568G>A (p.V190M) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a G to A substitution at nucleotide position 568, causing the valine (V) at amino acid position 190 to be replaced by a methionine (M). 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	0.096
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.27
DANN	Benign	0.13
DEOGEN2	Benign	0.0029	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.0040
Sift	Benign	0.36	T
Sift4G	Benign	0.25	T
Polyphen		0.0090	B
Vest4		0.22
MutPred		0.23		Loss of sheet (P = 0.0315);
MVP		0.14
MPC		0.64
ClinPred		0.039	T
GERP RS		-1.6
Varity_R		0.045
gMVP		0.017

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-102528924;