Variant X-103331528-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_152278.5(TCEAL7):c.125T>C(p.Leu42Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,207,050 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000021 ( 0 hom. 9 hem. )

Consequence

TCEAL7
NM_152278.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.867

Variant links:

Genes affected

TCEAL7 (HGNC:28336): (transcription elongation factor A like 7) Predicted to enable WW domain binding activity. Involved in negative regulation of NF-kappaB transcription factor activity and negative regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TCEAL7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL7	NM_152278.5 link	c.125T>C	p.Leu42Pro	missense_variant	3/3	ENST00000332431.5	NP_689491.1
TCEAL7	NM_001348258.2 link	c.125T>C	p.Leu42Pro	missense_variant	3/3		NP_001335187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL7	ENST00000332431.5 link	c.125T>C	p.Leu42Pro	missense_variant	3/3	1	NM_152278.5	ENSP00000329794.4		Q9BRU2
TCEAL7	ENST00000372666.1 link	c.125T>C	p.Leu42Pro	missense_variant	3/3	2		ENSP00000361751.1		Q9BRU2

Frequencies

GnomAD3 genomes

AF:

0.0000362

AC:

AN:

110582

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32780

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:

0.0000755

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

181249

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67113

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:

0.0000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1096468

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

361878

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:

0.0000262

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000362

AC:

AN:

110582

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32780

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:

0.0000755

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Nov 27, 2024

The c.125T>C (p.L42P) alteration is located in exon 3 (coding exon 1) of the TCEAL7 gene. This alteration results from a T to C substitution at nucleotide position 125, causing the leucine (L) at amino acid position 42 to be replaced by a proline (P). 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

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.50

.;T

M_CAP

Benign

0.0040

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.17

Sift

Benign

0.096

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.99

D;D

Vest4

0.70

MutPred

0.48

Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);

MVP

0.26

MPC

1.6

ClinPred

0.48

GERP RS

4.1

Varity_R

0.80

gMVP

0.64

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