X-103357814-A-T

Position:

chrX-103357814-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016303.3(TCEAL9):c.130A>T(p.Thr44Ser) 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 1,209,822 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 5 hem. )

Consequence

TCEAL9
NM_016303.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

TCEAL9 (HGNC:30084): (transcription elongation factor A like 9) The globular WW domain is composed of 38 to 40 semiconserved amino acids shared by proteins of diverse functions including structural, regulatory, and signaling proteins. The domain is involved in mediating protein-protein interactions through the binding of polyproline ligands. This gene encodes a WW domain binding protein. This gene also encodes a domain with similarity to the transcription elongation factor A, SII-related family. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

TCEAL9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038300335).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TCEAL9	NM_016303.3 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	3/3	ENST00000372661.6	NP_057387.1
TCEAL9	NM_001006612.2 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	3/3		NP_001006613.1
TCEAL9	NM_001006613.2 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	2/2		NP_001006614.1
TCEAL9	NM_001006614.2 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	2/2		NP_001006615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TCEAL9	ENST00000372661.6 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	3/3	1	NM_016303.3	ENSP00000361745	P1
TCEAL9	ENST00000372656.5 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	2/2	2		ENSP00000361740	P1
TCEAL9	ENST00000646896.1 linkuse as main transcript	c.130A>T	p.Thr44Ser	missense_variant	1/1			ENSP00000496422	P1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111589

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33749

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183334

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1098233

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363595

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000950

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111589

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33749

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.130A>T (p.T44S) alteration is located in exon 3 (coding exon 1) of the TCEAL9 gene. This alteration results from a A to T substitution at nucleotide position 130, causing the threonine (T) at amino acid position 44 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

0.088

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.98

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.0054

T;T;T

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.16

.;.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.44

N;N;.

REVEL

Benign

0.024

Sift

Benign

0.87

T;T;.

Sift4G

Benign

0.64

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.12

MutPred

0.22

Loss of methylation at K42 (P = 0.0848);Loss of methylation at K42 (P = 0.0848);Loss of methylation at K42 (P = 0.0848);

MVP

0.18

MPC

0.049

ClinPred

0.032

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.11

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