Genetic Variant TCEAL2:p.Ile134Val (chrX-102127230-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_080390.4(TCEAL2):c.400A>G(p.Ile134Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,209,256 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 122 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., 18 hem., cov: 22)

Exomes 𝑓: 0.00028 ( 0 hom. 104 hem. )

Consequence

TCEAL2
NM_080390.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.364

Publications

0 publications found

Variant links:

Genes affected

TCEAL2 (HGNC:29818): (transcription elongation factor A like 2) 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. [provided by RefSeq, Jul 2008]

TCEAL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006099552).

BP6

Variant X-102127230-A-G is Benign according to our data. Variant chrX-102127230-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2307557.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080390.4. 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
	TCEAL2	NM_080390.4	MANE Select	c.400A>G	p.Ile134Val	missense	Exon 3 of 3	NP_525129.1	Q9H3H9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCEAL2	ENST00000372780.6	TSL:1 MANE Select	c.400A>G	p.Ile134Val	missense	Exon 3 of 3	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000329035.2	TSL:5	c.400A>G	p.Ile134Val	missense	Exon 3 of 3	ENSP00000332359.2	Q9H3H9
TCEAL2	ENST00000902218.1		c.400A>G	p.Ile134Val	missense	Exon 3 of 3	ENSP00000572277.1

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

AN:

110966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

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:

0.000340

Gnomad OTH

AF:

0.000665

GnomAD2 exomes

AF:

0.000273

AC:

AN:

182979

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.000305

Gnomad AMR exome

AF:

0.000949

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000278

AC:

305

AN:

1098233

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

104

AN XY:

363589

show subpopulations

African (AFR)

AF:

0.000379

AC:

AN:

26403

American (AMR)

AF:

0.000881

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000295

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000274

AC:

231

AN:

842145

Other (OTH)

AF:

0.000347

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

100

<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:

0.000730

AC:

AN:

111023

Hom.:

Cov.:

AF XY:

0.000542

AC XY:

AN XY:

33231

show subpopulations

African (AFR)

AF:

0.000621

AC:

AN:

30583

American (AMR)

AF:

0.00412

AC:

AN:

10435

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2631

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2533

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000340

AC:

AN:

52926

Other (OTH)

AF:

0.000657

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000884

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.081

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.015

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.00024

LIST_S2

Benign

0.11

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.0

PhyloP100

-0.36

PrimateAI

Benign

0.38

PROVEAN

Benign

0.65

REVEL

Benign

0.021

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.037

MVP

0.043

MPC

0.079

ClinPred

0.0034

GERP RS

-1.6

Varity_R

0.035

gMVP

0.0077

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over