dbSNP rs201161155: TCEAL2:p.Phe5Tyr (chrX-102126844-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F5C) has been classified as Likely benign.

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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031745046).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080390.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL2	NM_080390.4	MANE Select	c.14T>A	p.Phe5Tyr	missense	Exon 3 of 3	NP_525129.1	Q9H3H9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCEAL2	ENST00000372780.6	TSL:1 MANE Select	c.14T>A	p.Phe5Tyr	missense	Exon 3 of 3	ENSP00000361866.1	Q9H3H9
TCEAL2	ENST00000476749.1	TSL:1	n.799T>A		non_coding_transcript_exon	Exon 2 of 2
TCEAL2	ENST00000329035.2	TSL:5	c.14T>A	p.Phe5Tyr	missense	Exon 3 of 3	ENSP00000332359.2	Q9H3H9

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112249

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

175852

AF XY:

0.0000482

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 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

African (AFR)

AF:

0.00

AC:

AN:

25772

American (AMR)

AF:

0.0000296

AC:

AN:

33764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19042

East Asian (EAS)

AF:

0.00

AC:

AN:

30167

South Asian (SAS)

AF:

0.00

AC:

AN:

52660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40409

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.000155

AC:

130

AN:

839958

Other (OTH)

AF:

0.0000656

AC:

AN:

45702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112304

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30934

American (AMR)

AF:

0.0000938

AC:

AN:

10666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2697

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53192

Other (OTH)

AF:

0.00

AC:

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.024

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.0018

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.078

M_CAP

Benign

0.00057

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

PhyloP100

-0.55

PrimateAI

Benign

0.43

PROVEAN

Benign

1.0

REVEL

Benign

0.0010

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.072

MutPred

0.27

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over