Variant X-103331615-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000332431.5(TCEAL7):c.212G>A(p.Arg71Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,206,746 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 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 0.000054 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000014 ( 0 hom. 4 hem. )

Consequence

TCEAL7
ENST00000332431.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056474745).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL7	NM_152278.5 linkuse as main transcript	c.212G>A	p.Arg71Lys	missense_variant	3/3	ENST00000332431.5	NP_689491.1
TCEAL7	NM_001348258.2 linkuse as main transcript	c.212G>A	p.Arg71Lys	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.212G>A	p.Arg71Lys	missense_variant	3/3	1	NM_152278.5	ENSP00000329794	P1
TCEAL7	ENST00000372666.1 linkuse as main transcript	c.212G>A	p.Arg71Lys	missense_variant	3/3	2		ENSP00000361751	P1

Frequencies

GnomAD3 genomes

AF:

0.0000541

AC:

AN:

110945

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

33143

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000958

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000847

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.0000551

AC:

AN:

181527

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67309

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000577

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1095748

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

361142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000431

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000541

AC:

AN:

110998

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

33206

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000957

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000850

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000168

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000659

Alfa

AF:

0.0000844

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000741

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

May 24, 2024

The c.212G>A (p.R71K) alteration is located in exon 3 (coding exon 1) of the TCEAL7 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the arginine (R) at amino acid position 71 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

0.097

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.58

.;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.21

T;T

Polyphen

0.99

D;D

Vest4

0.14

MutPred

0.67

Gain of methylation at R71 (P = 0.0097);Gain of methylation at R71 (P = 0.0097);

MVP

0.30

MPC

1.3

ClinPred

0.17

GERP RS

3.1

Varity_R

0.42

gMVP

0.65

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