X-103630329-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_004780.3(TCEAL1):c.413A>G(p.Lys138Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000479 in 1,210,364 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 16 hem. )

Consequence

TCEAL1
NM_004780.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37884066).

BP6

Variant X-103630329-A-G is Benign according to our data. Variant chrX-103630329-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2691408.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL1	NM_004780.3 link	c.413A>G	p.Lys138Arg	missense_variant	Exon 3 of 3	ENST00000372625.8	NP_004771.2	Q15170
TCEAL1	NM_001006639.2 link	c.413A>G	p.Lys138Arg	missense_variant	Exon 3 of 3		NP_001006640.1	Q15170
TCEAL1	NM_001006640.2 link	c.413A>G	p.Lys138Arg	missense_variant	Exon 3 of 3		NP_001006641.1	Q15170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCEAL1	ENST00000372625.8 link	c.413A>G	p.Lys138Arg	missense_variant	Exon 3 of 3	1	NM_004780.3	ENSP00000361708.3	Q15170
TCEAL1	ENST00000372624.3 link	c.413A>G	p.Lys138Arg	missense_variant	Exon 3 of 3	1		ENSP00000361707.3	Q15170
TCEAL1	ENST00000372626.7 link	c.413A>G	p.Lys138Arg	missense_variant	Exon 3 of 3	2		ENSP00000361709.3	Q15170
TCEAL1	ENST00000469820.1 link	n.*112A>G		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112442

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34586

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183005

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67467

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1097922

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

363280

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000618

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112442

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 26, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: TCEAL1 c.413A>G (p.Lys138Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 1210364 control chromosomes including 16 hemizygotes suggesting a benign role for the variant. To our knowledge, no occurrence of c.413A>G in individuals affected with Neurodevelopmental Disorder With Gait Disturbance, Dysmorphic Facies, And Behavioral Abnormalities, X-Linked and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.33

.;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.96

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.83

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.38

MutPred

0.44

Loss of ubiquitination at K138 (P = 0.0141);Loss of ubiquitination at K138 (P = 0.0141);Loss of ubiquitination at K138 (P = 0.0141);

MVP

0.92

MPC

1.7

ClinPred

0.43

GERP RS

4.7

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over