Genetic Variant TCEAL8:p.Glu39Lys (chrX-103253865-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153333.3(TCEAL8):c.115G>A(p.Glu39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,210,802 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000014 ( 0 hom. 7 hem. )

Consequence

TCEAL8
NM_153333.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.673

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03555265).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153333.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL8	NM_153333.3	MANE Select	c.115G>A	p.Glu39Lys	missense	Exon 3 of 3	NP_699164.1	Q8IYN2
	TCEAL8	NM_001006684.2		c.115G>A	p.Glu39Lys	missense	Exon 2 of 2	NP_001006685.1	Q8IYN2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCEAL8	ENST00000372685.8	TSL:1 MANE Select	c.115G>A	p.Glu39Lys	missense	Exon 3 of 3	ENSP00000361770.3	Q8IYN2
TCEAL8	ENST00000360000.8	TSL:1	c.115G>A	p.Glu39Lys	missense	Exon 2 of 2	ENSP00000353093.4	Q8IYN2
TCEAL8	ENST00000866567.1		c.115G>A	p.Glu39Lys	missense	Exon 3 of 3	ENSP00000536626.1

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112589

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.000657

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

183441

AF XY:

0.0000589

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1098213

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363567

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.000259

AC:

AN:

54148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

842101

Other (OTH)

AF:

0.00

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000888

AC:

AN:

112589

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34719

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31002

American (AMR)

AF:

0.00

AC:

AN:

10717

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3584

South Asian (SAS)

AF:

0.00

AC:

AN:

2709

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6171

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53301

Other (OTH)

AF:

0.000657

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.4

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.78

M_CAP

Benign

0.0031

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

PhyloP100

-0.67

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

REVEL

Benign

0.029

Sift

Benign

0.67

Sift4G

Benign

0.064

Polyphen

0.026

Vest4

0.095

MutPred

0.46

Gain of ubiquitination at E39 (P = 0.0054)

MVP

0.014

MPC

0.49

ClinPred

0.042

GERP RS

-0.69

Varity_R

0.069

gMVP

0.35

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over