X-103630237-TCGTTCTCGCC-T

Position:

• chrX-103630237-TCGTTCTCGCC-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_004780.3(TCEAL1):​c.324_333del​(p.Ser109AsnfsTer11) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL1 NM_004780.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.65

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 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 0.329 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-103630237-TCGTTCTCGCC-T is Pathogenic according to our data. Variant chrX-103630237-TCGTTCTCGCC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2673277.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL1	NM_004780.3	c.324_333del	p.Ser109AsnfsTer11	frameshift_variant	3/3	ENST00000372625.8	NP_004771.2
TCEAL1	NM_001006639.2	c.324_333del	p.Ser109AsnfsTer11	frameshift_variant	3/3		NP_001006640.1
TCEAL1	NM_001006640.2	c.324_333del	p.Ser109AsnfsTer11	frameshift_variant	3/3		NP_001006641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL1	ENST00000372625.8	c.324_333del	p.Ser109AsnfsTer11	frameshift_variant	3/3	1	NM_004780.3	ENSP00000361708	P1
TCEAL1	ENST00000372624.3	c.324_333del	p.Ser109AsnfsTer11	frameshift_variant	3/3	1		ENSP00000361707	P1
TCEAL1	ENST00000372626.7	c.324_333del	p.Ser109AsnfsTer11	frameshift_variant	3/3	2		ENSP00000361709	P1
TCEAL1	ENST00000469820.1			downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely pathogenic, criteria provided, single submitter

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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-102885165;