dbSNP rs751158666: TCEAL3:p.Ser65Asn (chrX-103609258-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_032926.3(TCEAL3):c.194G>A(p.Ser65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,209,773 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 (★).

Frequency

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

Exomes 𝑓: 0.0000082 ( 0 hom. 4 hem. )

Consequence

TCEAL3
NM_032926.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.331

Publications

0 publications found

Variant links:

Genes affected

TCEAL3 (HGNC:28247): (transcription elongation factor A like 3) 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. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

TCEAL3 links:

ENSG00000304280 (HGNC:):

ENSG00000304280 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity TCAL3_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0197635).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032926.3. 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
	TCEAL3	NM_032926.3	MANE Select	c.194G>A	p.Ser65Asn	missense	Exon 3 of 3	NP_116315.1	Q969E4
	TCEAL3	NM_001006933.2		c.194G>A	p.Ser65Asn	missense	Exon 3 of 3	NP_001006934.1	Q969E4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCEAL3	ENST00000372627.10	TSL:1 MANE Select	c.194G>A	p.Ser65Asn	missense	Exon 3 of 3	ENSP00000361710.5	Q969E4
TCEAL3	ENST00000243286.7	TSL:1	c.194G>A	p.Ser65Asn	missense	Exon 3 of 3	ENSP00000243286.3	Q969E4
TCEAL3	ENST00000372628.5	TSL:5	c.194G>A	p.Ser65Asn	missense	Exon 3 of 3	ENSP00000361711.1	Q969E4

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000285

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

183415

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000820

AC:

AN:

1098176

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363538

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26399

American (AMR)

AF:

0.0000284

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.0000993

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54135

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

842095

Other (OTH)

AF:

0.00

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.0000179

AC:

AN:

111597

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33785

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30751

American (AMR)

AF:

0.00

AC:

AN:

10607

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.000286

AC:

AN:

3495

South Asian (SAS)

AF:

0.000380

AC:

AN:

2629

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52970

Other (OTH)

AF:

0.00

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

0.059

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-1.1

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0045

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.36

M_CAP

Benign

0.0025

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.33

PrimateAI

Benign

0.31

PROVEAN

Benign

0.30

REVEL

Benign

0.012

Sift

Benign

0.12

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.018

MutPred

0.34

Loss of phosphorylation at S65 (P = 0.0016)

MVP

0.043

MPC

0.79

ClinPred

0.0075

GERP RS

-3.0

Varity_R

0.070

gMVP

0.0074

Mutation Taster

=100/0

polymorphism

(source)

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

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