Variant X-103630175-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_004780.3(TCEAL1):c.259C>T(p.Gln87Ter) 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

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 1.74

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 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. Fraction of 0.46 CDS is truncated, and there are 1 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-103630175-C-T is Pathogenic according to our data. Variant chrX-103630175-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1700031.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-103630175-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TCEAL1	NM_004780.3 linkuse as main transcript	c.259C>T	p.Gln87Ter	stop_gained	3/3	ENST00000372625.8	NP_004771.2
TCEAL1	NM_001006639.2 linkuse as main transcript	c.259C>T	p.Gln87Ter	stop_gained	3/3		NP_001006640.1
TCEAL1	NM_001006640.2 linkuse as main transcript	c.259C>T	p.Gln87Ter	stop_gained	3/3		NP_001006641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TCEAL1	ENST00000372625.8 linkuse as main transcript	c.259C>T	p.Gln87Ter	stop_gained	3/3	1	NM_004780.3	ENSP00000361708	P1
TCEAL1	ENST00000372624.3 linkuse as main transcript	c.259C>T	p.Gln87Ter	stop_gained	3/3	1		ENSP00000361707	P1
TCEAL1	ENST00000469820.1 linkuse as main transcript	n.724C>T		non_coding_transcript_exon_variant	2/2	1
TCEAL1	ENST00000372626.7 linkuse as main transcript	c.259C>T	p.Gln87Ter	stop_gained	3/3	2		ENSP00000361709	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 12, 2023

- -

See cases

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

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

Aug 02, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.69

MutationTaster

Benign

1.0

D;D;D

Vest4

0.34

GERP RS

4.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over