dbSNP rs184347611: TCEAL2:p.Glu119Gly (chrX-102127186-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_080390.4(TCEAL2):c.356A>G(p.Glu119Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,209,037 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 51 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00014 ( 0 hom. 49 hem. )

Consequence

TCEAL2
NM_080390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.15

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037735224).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4 link	c.356A>G	p.Glu119Gly	missense_variant	Exon 3 of 3	ENST00000372780.6	NP_525129.1	Q9H3H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCEAL2	ENST00000372780.6 link	c.356A>G	p.Glu119Gly	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000329035.2 link	c.356A>G	p.Glu119Gly	missense_variant	Exon 3 of 3	5		ENSP00000332359.2	Q9H3H9
TCEAL2	ENST00000651085.1 link	n.153+741A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000903

AC:

AN:

110763

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

32985

show subpopulations

Gnomad AFR

AF:

0.0000658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000962

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000929

AC:

AN:

182950

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

67568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000981

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

149

AN:

1098221

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

363591

show subpopulations

Gnomad4 AFR exome

AF:

0.0000757

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.0000902

AC:

AN:

110816

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

33048

show subpopulations

Gnomad4 AFR

AF:

0.0000656

Gnomad4 AMR

AF:

0.0000961

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.356A>G (p.E119G) alteration is located in exon 3 (coding exon 1) of the TCEAL2 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the glutamic acid (E) at amino acid position 119 to be replaced by a glycine (G). 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

Benign

0.074

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.10

T;.

M_CAP

Benign

0.0038

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.021

Sift

Benign

0.15

T;T

Sift4G

Benign

0.090

T;T

Polyphen

0.50

P;P

Vest4

0.027

MVP

0.068

MPC

0.39

ClinPred

0.052

GERP RS

-0.65

Varity_R

0.093

gMVP

0.015

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