Genetic Variant TCEAL8:p.Gln103Lys (chrX-103253673-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153333.3(TCEAL8):c.307C>A(p.Gln103Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,210,529 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000053 ( 0 hom. 31 hem. )

Consequence

TCEAL8
NM_153333.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57

Variant links:

Genes affected

TCEAL8 (HGNC:28683): (transcription elongation factor A like 8) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family contain TFA domains and may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. 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]

TCEAL8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032323748).

BS2

High Hemizygotes in GnomAdExome4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL8	NM_153333.3 link	c.307C>A	p.Gln103Lys	missense_variant	Exon 3 of 3	ENST00000372685.8	NP_699164.1	Q8IYN2
TCEAL8	NM_001006684.2 link	c.307C>A	p.Gln103Lys	missense_variant	Exon 2 of 2		NP_001006685.1	Q8IYN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCEAL8	ENST00000372685.8 link	c.307C>A	p.Gln103Lys	missense_variant	Exon 3 of 3	1	NM_153333.3	ENSP00000361770.3	Q8IYN2
TCEAL8	ENST00000360000.8 link	c.307C>A	p.Gln103Lys	missense_variant	Exon 2 of 2	1		ENSP00000353093.4	Q8IYN2
TCEAL8	ENST00000451678.1 link	c.208C>A	p.Gln70Lys	missense_variant	Exon 4 of 4	3		ENSP00000390880.1	Q5H9L1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112654

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

34806

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:

0.000738

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

181158

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

66714

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:

0.00127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000528

AC:

AN:

1097820

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

363188

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:

0.000943

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112709

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

34871

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:

0.000740

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.307C>A (p.Q103K) alteration is located in exon 3 (coding exon 1) of the TCEAL8 gene. This alteration results from a C to A substitution at nucleotide position 307, causing the glutamine (Q) at amino acid position 103 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.69

.;T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.52

T;T;T

Sift4G

Benign

0.62

T;T;.

Polyphen

0.99

D;D;.

Vest4

0.20

MutPred

0.52

Gain of methylation at Q103 (P = 0.0095);Gain of methylation at Q103 (P = 0.0095);.;

MVP

0.12

MPC

1.2

ClinPred

0.22

GERP RS

4.5

Varity_R

0.29

gMVP

0.63

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