Variant 1-235433008-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003193.5(TBCE):c.661-1196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,521,900 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 137 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 96 hom. )

Consequence

TBCE
NM_003193.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0190

Variant links:

Genes affected

TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

TBCE links:

RPS21P1 (HGNC:36401): (ribosomal protein S21 pseudogene 1)

RPS21P1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-235433008-C-T is Benign according to our data. Variant chr1-235433008-C-T is described in ClinVar as [Benign]. Clinvar id is 1270754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235433008-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBCE	NM_003193.5 linkuse as main transcript	c.661-1196C>T		intron_variant		ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2 linkuse as main transcript	c.723C>T	p.Phe241=	synonymous_variant	8/18		NP_001274730.1
TBCE	NM_001079515.3 linkuse as main transcript	c.661-1196C>T		intron_variant			NP_001072983.1
TBCE	NM_001287802.2 linkuse as main transcript	c.322-1196C>T		intron_variant			NP_001274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2 linkuse as main transcript	c.661-1196C>T		intron_variant			NM_003193.5	ENSP00000494796	P1	Q15813-1
RPS21P1	ENST00000434479.2 linkuse as main transcript	n.24C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3371

AN:

151530

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00810

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00433

AC:

563

AN:

130050

Hom.:

AF XY:

0.00353

AC XY:

252

AN XY:

71396

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.00469

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000959

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000539

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.00225

AC:

3077

AN:

1370260

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1316

AN XY:

676288

show subpopulations

Gnomad4 AFR exome

AF:

0.0753

Gnomad4 AMR exome

AF:

0.00475

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000288

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000253

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.0223

AC:

3388

AN:

151640

Hom.:

137

Cov.:

AF XY:

0.0217

AC XY:

1608

AN XY:

74040

show subpopulations

Gnomad4 AFR

AF:

0.0772

Gnomad4 AMR

AF:

0.00809

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.0186

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.1

DANN

Benign

0.77

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