Variant 8-53988219-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006756.4(TCEA1):c.361A>G(p.Asn121Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,613,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

TCEA1
NM_006756.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048327476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCEA1	NM_006756.4 linkuse as main transcript	c.361A>G	p.Asn121Asp	missense_variant	5/10	ENST00000521604.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCEA1	ENST00000521604.7 linkuse as main transcript	c.361A>G	p.Asn121Asp	missense_variant	5/10	1	NM_006756.4	P1	P23193-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000685

AC:

AN:

248222

Hom.:

AF XY:

0.0000817

AC XY:

AN XY:

134682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000999

AC:

146

AN:

1461324

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

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

Feb 28, 2023

The c.361A>G (p.N121D) alteration is located in exon 5 (coding exon 5) of the TCEA1 gene. This alteration results from a A to G substitution at nucleotide position 361, causing the asparagine (N) at amino acid position 121 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

Benign

0.071

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.048

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.040

N;N;.;.

REVEL

Benign

0.031

Sift

Benign

0.81

T;T;.;.

Sift4G

Benign

0.67

T;T;.;.

Polyphen

0.0

B;B;.;.

Vest4

0.30

MVP

0.52

MPC

0.11

ClinPred

0.034

GERP RS

3.2

Varity_R

0.028

gMVP

0.11

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