X-103609258-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -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. 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., 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL3	NM_032926.3 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 3	ENST00000372627.10	NP_116315.1	Q969E4
TCEAL3	NM_001006933.2 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 3		NP_001006934.1	Q969E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCEAL3	ENST00000372627.10 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 3	1	NM_032926.3	ENSP00000361710.5	Q969E4
TCEAL3	ENST00000243286.7 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 3	1		ENSP00000243286.3	Q969E4
TCEAL3	ENST00000372628.5 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 3	5		ENSP00000361711.1	Q969E4
TCEAL3	ENST00000477014.1 link	n.158+585G>A		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111546

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33724

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

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183415

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67845

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 SAS exome

AF:

0.0000524

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

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000993

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111597

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33785

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000286

Gnomad4 SAS

AF:

0.000380

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.194G>A (p.S65N) alteration is located in exon 3 (coding exon 1) of the TCEAL3 gene. This alteration results from a G to A substitution at nucleotide position 194, causing the serine (S) at amino acid position 65 to be replaced by an asparagine (N). 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

-0.78

BayesDel_noAF

Benign

-1.1

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0045

T;T;T

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.36

.;T;.

M_CAP

Benign

0.0025

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.30

N;N;N

REVEL

Benign

0.012

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.018

MutPred

0.34

Loss of phosphorylation at S65 (P = 0.0016);Loss of phosphorylation at S65 (P = 0.0016);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

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