Variant rs767004810 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PM4PP5_Very_Strong

The NM_003193.5(TBCE):c.155_166del(p.Ser52_Gly55del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000558 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TBCE
NM_003193.5 inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:14

Conservation

PhyloP100: 5.97

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:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_003193.5.

PP5

Variant 1-235401552-TGGGAGCCACGAA-T is Pathogenic according to our data. Variant chr1-235401552-TGGGAGCCACGAA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 5290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235401552-TGGGAGCCACGAA-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBCE	NM_003193.5 linkuse as main transcript	c.155_166del	p.Ser52_Gly55del	inframe_deletion	3/17	ENST00000642610.2	NP_003184.1
TBCE	NM_001079515.3 linkuse as main transcript	c.155_166del	p.Ser52_Gly55del	inframe_deletion	3/17		NP_001072983.1
TBCE	NM_001287801.2 linkuse as main transcript	c.155_166del	p.Ser52_Gly55del	inframe_deletion	3/18		NP_001274730.1
TBCE	NM_001287802.2 linkuse as main transcript	c.-210-12876_-210-12865del		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.155_166del	p.Ser52_Gly55del	inframe_deletion	3/17		NM_003193.5	ENSP00000494796	P1	Q15813-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152166

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251482

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135912

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461666

Hom.:

AF XY:

0.00000688

AC XY:

AN XY:

727128

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000756

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypoparathyroidism-retardation-dysmorphism syndrome

Pathogenic:8

Pathogenic, criteria provided, single submitter	clinical testing	3billion	May 22, 2022	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:12389028). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID:12389028, 20152369, 25097779, 26231322, 26336027, 30080992, 30638765). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. -
Likely pathogenic, criteria provided, single submitter	clinical testing	Centre for Translational Omics - GOSgene, University College London	Mar 16, 2018	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 2002	- -
Pathogenic, criteria provided, single submitter	clinical testing	Centogene AG - the Rare Disease Company	Jul 20, 2021	- -
Pathogenic, no assertion criteria provided	clinical testing	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	Feb 05, 2020	- -
Pathogenic, criteria provided, single submitter	clinical testing	Pathology and Clinical Laboratory Medicine, King Fahad Medical City	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	Apr 01, 2023	- -
Pathogenic, criteria provided, single submitter	clinical testing	Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	Dec 30, 2017	- -

not provided

Pathogenic:4

Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 13, 2023	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 5290). This variant has been observed in individuals with hypoparathyroidism-retardation-dysmorphism syndrome (PMID: 12389028, 20152369, 26231322, 30080992). It is commonly reported in individuals of Middle Eastern ancestry (PMID: 12389028, 30080992). This variant is present in population databases (rs767004810, gnomAD 0.006%). This variant, c.155_166del, results in the deletion of 4 amino acid(s) of the TBCE protein (p.Ser52_Gly55del), but otherwise preserves the integrity of the reading frame. -
Pathogenic, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 18, 2014	- -
Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2024	In-frame deletion of 4 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30080992, 29620724, 20152369, 26336027, 25097779, 30049826, 30638765, 26231322, 31589614, 36258138, 34374989, 35935360, 12389028) -
Pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Jan 18, 2022	- -

Encephalopathy, progressive, with amyotrophy and optic atrophy

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 25, 2024

- -

Autosomal recessive Kenny-Caffey syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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