NM_004780.3:c.196G>T

Variant names:

• chrX-103630112-G-T
• rs1603180742
• NM_004780.3:c.196G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_004780.3(TCEAL1):​c.196G>T​(p.Glu66*) 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 benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL1 NM_004780.3 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

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]

TCEAL1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 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. There are 9 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-103630112-G-T is Pathogenic according to our data. Variant chrX-103630112-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3175047.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004780.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL1	NM_004780.3	MANE Select	c.196G>T	p.Glu66*	stop_gained	Exon 3 of 3	NP_004771.2	Q15170
	TCEAL1	NM_001006639.2		c.196G>T	p.Glu66*	stop_gained	Exon 3 of 3	NP_001006640.1	Q15170
	TCEAL1	NM_001006640.2		c.196G>T	p.Glu66*	stop_gained	Exon 3 of 3	NP_001006641.1	Q15170

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL1	ENST00000372625.8	TSL:1 MANE Select	c.196G>T	p.Glu66*	stop_gained	Exon 3 of 3	ENSP00000361708.3	Q15170
	TCEAL1	ENST00000372624.3	TSL:1	c.196G>T	p.Glu66*	stop_gained	Exon 3 of 3	ENSP00000361707.3	Q15170
	TCEAL1	ENST00000469820.1	TSL:1	n.661G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	35
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.81	D
PhyloP100		2.3
Vest4		0.31
ClinPred		1.0	D
GERP RS		2.8
Mutation Taster		=117/83	polymorphism

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

Other links and lift over

dbSNP: rs1603180742; hg19: chrX-102885040;