Genetic Variant TCEAL2:p.Ile18Thr (chrX-102126883-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080390.4(TCEAL2):c.53T>C(p.Ile18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,126 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 24)

Consequence

TCEAL2
NM_080390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.751

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04610333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4 link	c.53T>C	p.Ile18Thr	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.53T>C	p.Ile18Thr	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000476749.1 link	n.838T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
TCEAL2	ENST00000329035.2 link	c.53T>C	p.Ile18Thr	missense_variant	Exon 3 of 3	5		ENSP00000332359.2	Q9H3H9
TCEAL2	ENST00000651085.1 link	n.153+438T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112126

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34368

show subpopulations

Gnomad AFR

AF:

0.0000649

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112126

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34368

show subpopulations

Gnomad4 AFR

AF:

0.0000649

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53T>C (p.I18T) alteration is located in exon 3 (coding exon 1) of the TCEAL2 gene. This alteration results from a T to C substitution at nucleotide position 53, causing the isoleucine (I) at amino acid position 18 to be replaced by a threonine (T). 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

0.053

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.40

DANN

Benign

0.78

DEOGEN2

Benign

0.0032

T;T

FATHMM_MKL

Benign

0.0093

LIST_S2

Benign

0.13

T;.

M_CAP

Benign

0.00092

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.0080

Sift

Benign

0.33

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.023

B;B

Vest4

0.063

MutPred

0.40

Loss of stability (P = 0.0128);Loss of stability (P = 0.0128);

MVP

0.043

MPC

0.17

ClinPred

0.044

GERP RS

1.6

Varity_R

0.035

gMVP

0.013

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