Genetic Variant TCEAL6:p.Asp119Glu (chrX-102140975-G-T) – 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_001006938.3(TCEAL6):c.357C>A(p.Asp119Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

TCEAL6
NM_001006938.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.89

Variant links:

Genes affected

TCEAL6 (HGNC:24553): (transcription elongation factor A like 6) Predicted to enable WW domain binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCEAL6 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=0.121123165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL6	NM_001006938.3 link	c.357C>A	p.Asp119Glu	missense_variant	Exon 3 of 3		NP_001006939.2	A0A024RCH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL6	ENST00000372774.8 link	c.357C>A	p.Asp119Glu	missense_variant	Exon 3 of 4	1		ENSP00000361860.4		Q6IPX3
TCEAL6	ENST00000372773.2 link	c.357C>A	p.Asp119Glu	missense_variant	Exon 3 of 4	3		ENSP00000361859.2		Q6IPX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183448

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000182

AC:

AN:

1098177

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363551

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.357C>A (p.D119E) alteration is located in exon 3 (coding exon 1) of the TCEAL6 gene. This alteration results from a C to A substitution at nucleotide position 357, causing the aspartic acid (D) at amino acid position 119 to be replaced by a glutamic acid (E). 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

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0010

DANN

Benign

0.28

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.66

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.089

Sift

Benign

0.37

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.99

D;D

Vest4

0.071

MutPred

0.23

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.17

MPC

0.19

ClinPred

0.15

GERP RS

-5.5

gMVP

0.0042

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