Genetic Variant ENST00000372774.8:c.41A>T (chrX-102141291-T-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000372774.8(TCEAL6):c.41A>T(p.Asn14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,095,615 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. 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: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 11 hem. )

Consequence

TCEAL6
ENST00000372774.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07026985).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL6	NM_001006938.3 link	c.41A>T	p.Asn14Ile	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.41A>T	p.Asn14Ile	missense_variant	Exon 3 of 4	1		ENSP00000361860.4		Q6IPX3
TCEAL6	ENST00000372773.2 link	c.41A>T	p.Asn14Ile	missense_variant	Exon 3 of 4	3		ENSP00000361859.2		Q6IPX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

176068

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

61996

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:

0.0000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1095615

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

361547

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:

0.0000178

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41A>T (p.N14I) alteration is located in exon 3 (coding exon 1) of the TCEAL6 gene. This alteration results from a A to T substitution at nucleotide position 41, causing the asparagine (N) at amino acid position 14 to be replaced by an isoleucine (I). 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

-0.51

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.57

DANN

Benign

0.93

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.11

.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.037

Sift

Benign

0.10

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0010

B;B

Vest4

0.17

MutPred

0.34

Gain of catalytic residue at N14 (P = 0.0664);Gain of catalytic residue at N14 (P = 0.0664);

MVP

0.082

MPC

0.21

ClinPred

0.10

GERP RS

-1.8

gMVP

0.016

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