Variant 8-53988235-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006756.4(TCEA1):c.345C>A(p.Asn115Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,613,510 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 4 hom. )

Consequence

TCEA1
NM_006756.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

Variant links:

Genes affected

TCEA1 (HGNC:11612): (transcription elongation factor A1) Predicted to enable DNA binding activity; translation elongation factor activity; and zinc ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within erythrocyte differentiation and positive regulation of transcription, DNA-templated. Located in nucleolus and nucleoplasm. Part of transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

TCEA1 links:

TCEA1 (HGNC:):

TCEA1 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=0.006788105).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEA1	NM_006756.4 linkuse as main transcript	c.345C>A	p.Asn115Lys	missense_variant	5/10	ENST00000521604.7	NP_006747.1	P23193-1A0A384MTX4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEA1	ENST00000521604.7 linkuse as main transcript	c.345C>A	p.Asn115Lys	missense_variant	5/10	1	NM_006756.4	ENSP00000428426.2		P23193-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152184

Hom.:

Cov.:

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:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

248370

Hom.:

AF XY:

0.000356

AC XY:

AN XY:

134768

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:

0.00209

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000125

AC:

182

AN:

1461208

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

726870

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:

0.00199

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74474

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:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000331

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 26, 2023

The c.345C>A (p.N115K) alteration is located in exon 5 (coding exon 5) of the TCEA1 gene. This alteration results from a C to A substitution at nucleotide position 345, causing the asparagine (N) at amino acid position 115 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

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.039

.;T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

0.016

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.69

T;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.0068

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

.;N;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

1.1

N;N;.;.

REVEL

Benign

0.15

Sift

Benign

0.95

T;T;.;.

Sift4G

Benign

0.99

T;T;.;.

Polyphen

0.0

B;B;.;.

Vest4

0.20

MutPred

0.34

.;Gain of ubiquitination at N115 (P = 7e-04);Gain of ubiquitination at N115 (P = 7e-04);.;

MVP

0.69

MPC

0.11

ClinPred

0.088

GERP RS

5.6

Varity_R

0.084

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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