Genetic Variant NM_153333.3:c.148C>G (chrX-103253832-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_153333.3(TCEAL8):c.148C>G(p.Pro50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,210,430 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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., 1 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 2 hem. )

Consequence

TCEAL8
NM_153333.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06954381).

BS2

High Hemizygotes in GnomAdExome4 at 2 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.148C>G	p.Pro50Ala	missense	Exon 3 of 3	NP_699164.1	Q8IYN2
	TCEAL8	NM_001006684.2		c.148C>G	p.Pro50Ala	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.148C>G	p.Pro50Ala	missense	Exon 3 of 3	ENSP00000361770.3	Q8IYN2
TCEAL8	ENST00000360000.8	TSL:1	c.148C>G	p.Pro50Ala	missense	Exon 2 of 2	ENSP00000353093.4	Q8IYN2
TCEAL8	ENST00000866567.1		c.148C>G	p.Pro50Ala	missense	Exon 3 of 3	ENSP00000536626.1

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112169

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

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:

0.00

GnomAD2 exomes

AF:

0.0000327

AC:

AN:

183471

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1098261

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363615

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.000170

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54149

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000831

AC:

AN:

842144

Other (OTH)

AF:

0.0000651

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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:

0.00000892

AC:

AN:

112169

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34331

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30850

American (AMR)

AF:

0.0000939

AC:

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00

AC:

AN:

2684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53213

Other (OTH)

AF:

0.00

AC:

AN:

1518

ExAC

AF:

0.00000824

AC:

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

0.079

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0079

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.72

M_CAP

Benign

0.0021

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Benign

0.25

PROVEAN

Benign

0.050

REVEL

Benign

0.055

Sift

Benign

0.045

Sift4G

Benign

0.55

Polyphen

0.0040

Vest4

0.20

MutPred

0.53

Loss of stability (P = 0.049)

MVP

0.11

MPC

0.40

ClinPred

0.041

GERP RS

4.4

Varity_R

0.081

gMVP

0.34

Mutation Taster

=99/1

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