chrX-103630363-G-A

Variant names:

• chrX-103630363-G-A
• NM_004780.3:c.447G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_004780.3(TCEAL1):​c.447G>A​(p.Trp149*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL1 NM_004780.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.92

Genes affected

TCEAL1 (HGNC:11616): (transcription elongation factor A like 1) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. The encoded protein is similar to transcription elongation factor A/transcription factor SII and contains a zinc finger-like motif as well as a sequence related to the transcription factor SII Pol II-binding region. It may exert its effects via protein-protein interactions with other transcriptional regulators rather than via direct binding of DNA. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0687 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-103630363-G-A is Pathogenic according to our data. Variant chrX-103630363-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1700029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-103630363-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL1	NM_004780.3	c.447G>A	p.Trp149*	stop_gained	Exon 3 of 3	ENST00000372625.8	NP_004771.2
TCEAL1	NM_001006639.2	c.447G>A	p.Trp149*	stop_gained	Exon 3 of 3		NP_001006640.1
TCEAL1	NM_001006640.2	c.447G>A	p.Trp149*	stop_gained	Exon 3 of 3		NP_001006641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL1	ENST00000372625.8	c.447G>A	p.Trp149*	stop_gained	Exon 3 of 3	1	NM_004780.3	ENSP00000361708.3
TCEAL1	ENST00000372624.3	c.447G>A	p.Trp149*	stop_gained	Exon 3 of 3	1		ENSP00000361707.3
TCEAL1	ENST00000372626.7	c.447G>A	p.Trp149*	stop_gained	Exon 3 of 3	2		ENSP00000361709.3
TCEAL1	ENST00000469820.1	n.*146G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked Pathogenic:1

Sep 12, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

See cases Pathogenic:1

Aug 02, 2022

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	37
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.72	D
Vest4		0.31
GERP RS		4.7

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-102885291;