Genetic Variant NM_080390.4:c.100T>C (chrX-102126930-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.100T>C(p.Cys34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,715 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

TCEAL2
NM_080390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.841

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:

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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=0.0610694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4 link	c.100T>C	p.Cys34Arg	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.100T>C	p.Cys34Arg	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000329035.2 link	c.100T>C	p.Cys34Arg	missense_variant	Exon 3 of 3	5		ENSP00000332359.2	Q9H3H9
TCEAL2	ENST00000651085.1 link	n.153+485T>C		intron_variant	Intron 2 of 3
TCEAL2	ENST00000476749.1 link	n.*30T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097715

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363089

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100T>C (p.C34R) 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 100, causing the cysteine (C) at amino acid position 34 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

DANN

Benign

0.64

DEOGEN2

Benign

0.023

T;T

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.66

T;.

M_CAP

Benign

0.0012

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.095

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.58

T;T

Polyphen

0.012

B;B

Vest4

0.24

MutPred

0.43

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.043

MPC

0.32

ClinPred

0.29

GERP RS

-2.3

Varity_R

0.63

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