dbSNP rs201161155: TCEAL2:p.Phe5Tyr (chrX-102126844-T-A) – 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.14T>A(p.Phe5Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,203,862 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 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 0.000045 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.00012 ( 0 hom. 42 hem. )

Consequence

TCEAL2
NM_080390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.550

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=0.031745046).

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.14T>A	p.Phe5Tyr	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.14T>A	p.Phe5Tyr	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000476749.1 link	n.799T>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
TCEAL2	ENST00000329035.2 link	c.14T>A	p.Phe5Tyr	missense_variant	Exon 3 of 3	5		ENSP00000332359.2	Q9H3H9
TCEAL2	ENST00000651085.1 link	n.153+399T>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112249

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34447

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

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:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

175852

Hom.:

AF XY:

0.0000482

AC XY:

AN XY:

62220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000386

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:

0.0000754

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

134

AN:

1091558

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

359426

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000296

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:

0.000155

Gnomad4 OTH exome

AF:

0.0000656

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112304

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000938

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ExAC

AF:

0.0000494

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.14T>A (p.F5Y) alteration is located in exon 3 (coding exon 1) of the TCEAL2 gene. This alteration results from a T to A substitution at nucleotide position 14, causing the phenylalanine (F) at amino acid position 5 to be replaced by a tyrosine (Y). 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

0.044

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.024

DANN

Benign

0.26

DEOGEN2

Benign

0.0018

T;T

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.078

T;.

M_CAP

Benign

0.00057

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.0010

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.072

MutPred

0.27

Gain of phosphorylation at F5 (P = 0.0273);Gain of phosphorylation at F5 (P = 0.0273);

MVP

0.043

MPC

0.15

ClinPred

0.022

GERP RS

-6.8

Varity_R

0.056

gMVP

0.0074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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