Variant chrX-103630185-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PS1_ModeratePM2PP5_ModerateBP4

The ENST00000372625.8(TCEAL1):c.269G>A(p.Cys90Tyr) 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. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 23)

Consequence

TCEAL1
ENST00000372625.8 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 1.85

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:

TCEAL1 (HGNC:):

TCEAL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PS1

Transcript ENST00000372625.8 (TCEAL1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-103630185-G-A is Pathogenic according to our data. Variant chrX-103630185-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1700032.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-103630185-G-A is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.2748689). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL1	NM_004780.3 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	3/3	ENST00000372625.8	NP_004771.2	Q15170
TCEAL1	NM_001006639.2 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	3/3		NP_001006640.1	Q15170
TCEAL1	NM_001006640.2 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	3/3		NP_001006641.1	Q15170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TCEAL1	ENST00000372625.8 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	3/3	1	NM_004780.3	ENSP00000361708.3	Q15170
TCEAL1	ENST00000372624.3 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	3/3	1		ENSP00000361707.3	Q15170
TCEAL1	ENST00000469820.1 linkuse as main transcript	n.734G>A		non_coding_transcript_exon_variant	2/2	1
TCEAL1	ENST00000372626.7 linkuse as main transcript	c.269G>A	p.Cys90Tyr	missense_variant	3/3	2		ENSP00000361709.3	Q15170

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

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.75

.;.;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.62

N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.084

T;T;T

Sift4G

Uncertain

0.059

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.26

MutPred

0.41

Gain of phosphorylation at C90 (P = 0.0056);Gain of phosphorylation at C90 (P = 0.0056);Gain of phosphorylation at C90 (P = 0.0056);

MVP

0.28

MPC

2.5

ClinPred

0.99

GERP RS

4.8

gMVP

0.11

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