Genetic Variant TCEAL3:p.Arg182Lys (chrX-103609609-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032926.3(TCEAL3):c.545G>A(p.Arg182Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,209,954 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 1 hem. )

Consequence

TCEAL3
NM_032926.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24557802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL3	NM_032926.3 link	c.545G>A	p.Arg182Lys	missense_variant	Exon 3 of 3	ENST00000372627.10	NP_116315.1	Q969E4
TCEAL3	NM_001006933.2 link	c.545G>A	p.Arg182Lys	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.545G>A	p.Arg182Lys	missense_variant	Exon 3 of 3	1	NM_032926.3	ENSP00000361710.5	Q969E4
TCEAL3	ENST00000243286.7 link	c.545G>A	p.Arg182Lys	missense_variant	Exon 3 of 3	1		ENSP00000243286.3	Q969E4
TCEAL3	ENST00000372628.5 link	c.545G>A	p.Arg182Lys	missense_variant	Exon 3 of 3	5		ENSP00000361711.1	Q969E4
TCEAL3	ENST00000477014.1 link	n.159-902G>A		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33830

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1098266

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363622

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:

0.00000895

AC:

AN:

111688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33830

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.545G>A (p.R182K) 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 545, causing the arginine (R) at amino acid position 182 to be replaced by a lysine (K). 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

0.26

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T;T

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.64

.;T;.

M_CAP

Benign

0.0066

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;M

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.094

Sift

Uncertain

0.022

D;D;D

Sift4G

Benign

0.067

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.18

MutPred

0.30

Gain of glycosylation at R182 (P = 0.0076);Gain of glycosylation at R182 (P = 0.0076);Gain of glycosylation at R182 (P = 0.0076);

MVP

0.24

MPC

0.87

ClinPred

0.56

GERP RS

3.7

Varity_R

0.25

gMVP

0.040

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