Genetic Variant NM_080390.4:c.17A>G (chrX-102126847-A-G) – 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.17A>G(p.Asn6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,204,239 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., 0 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

TCEAL2
NM_080390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.399

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=0.028759211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4 link	c.17A>G	p.Asn6Ser	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.17A>G	p.Asn6Ser	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000476749.1 link	n.802A>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
TCEAL2	ENST00000329035.2 link	c.17A>G	p.Asn6Ser	missense_variant	Exon 3 of 3	5		ENSP00000332359.2	Q9H3H9
TCEAL2	ENST00000651085.1 link	n.153+402A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

112706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34846

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000935

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

176144

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

62476

show subpopulations

Gnomad AFR exome

AF:

0.0000770

Gnomad AMR exome

AF:

0.0000772

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000275

AC:

AN:

1091533

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359345

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000593

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000177

AC:

AN:

112706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34846

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000935

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.17A>G (p.N6S) 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 17, causing the asparagine (N) at amino acid position 6 to be replaced by a serine (S). 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

0.059

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.017

DANN

Benign

0.15

DEOGEN2

Benign

0.0010

T;T

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.56

T;.

M_CAP

Benign

0.0011

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.93

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.024

Sift

Benign

0.59

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0010

B;B

Vest4

0.030

MVP

0.068

MPC

0.15

ClinPred

0.0072

GERP RS

-6.8

Varity_R

0.026

gMVP

0.0064

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