Variant X-103331628-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152278.5(TCEAL7):c.225G>T(p.Glu75Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,096,484 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000013 ( 0 hom. 8 hem. )

Consequence

TCEAL7
NM_152278.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.819

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3066187).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL7	NM_152278.5 linkuse as main transcript	c.225G>T	p.Glu75Asp	missense_variant	3/3	ENST00000332431.5	NP_689491.1
TCEAL7	NM_001348258.2 linkuse as main transcript	c.225G>T	p.Glu75Asp	missense_variant	3/3		NP_001335187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL7	ENST00000332431.5 linkuse as main transcript	c.225G>T	p.Glu75Asp	missense_variant	3/3	1	NM_152278.5	ENSP00000329794.4		Q9BRU2
TCEAL7	ENST00000372666.1 linkuse as main transcript	c.225G>T	p.Glu75Asp	missense_variant	3/3	2		ENSP00000361751.1		Q9BRU2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

181407

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67209

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:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1096484

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

361864

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:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

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

Jul 27, 2022

The c.225G>T (p.E75D) alteration is located in exon 3 (coding exon 1) of the TCEAL7 gene. This alteration results from a G to T substitution at nucleotide position 225, causing the glutamic acid (E) at amino acid position 75 to be replaced by an aspartic acid (D). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.21

MutPred

0.76

Gain of MoRF binding (P = 0.0989);Gain of MoRF binding (P = 0.0989);

MVP

0.24

MPC

0.96

ClinPred

0.87

GERP RS

2.1

Varity_R

0.72

gMVP

0.54

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