Genetic Variant TBCE:c.-31-60_-31-55delAAAAAA (chr1-235379947-CAAAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003193.5(TBCE):c.-31-60_-31-55delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 729,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

TBCE
NM_003193.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.566

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

hypoparathyroidism-retardation-dysmorphism syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
encephalopathy, progressive, with amyotrophy and optic atrophy
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen, G2P, Ambry Genetics
autosomal recessive Kenny-Caffey syndrome
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

TBCE links:

ENSG00000285053 (HGNC:):

ENSG00000285053 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003193.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBCE	NM_003193.5	MANE Select	c.-31-60_-31-55delAAAAAA	intron	N/A	NP_003184.1	Q15813-1
TBCE	NM_001287801.2		c.-31-60_-31-55delAAAAAA	intron	N/A	NP_001274730.1	Q15813-2
TBCE	NM_001079515.3		c.-31-60_-31-55delAAAAAA	intron	N/A	NP_001072983.1	Q15813-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBCE	ENST00000642610.2	MANE Select	c.-31-71_-31-66delAAAAAA	intron	N/A	ENSP00000494796.1	Q15813-1
ENSG00000285053	ENST00000647186.1		c.-31-71_-31-66delAAAAAA	intron	N/A	ENSP00000494775.1
TBCE	ENST00000366601.8	TSL:1	c.-31-71_-31-66delAAAAAA	intron	N/A	ENSP00000355560.4	A0A2U3TZJ6

Frequencies

GnomAD3 genomes

AF:

0.00000753

AC:

AN:

132774

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:

0.0000161

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000503

AC:

AN:

596382

Hom.:

AF XY:

0.00000319

AC XY:

AN XY:

313522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12778

American (AMR)

AF:

0.00

AC:

AN:

25028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14128

East Asian (EAS)

AF:

0.00

AC:

AN:

21036

South Asian (SAS)

AF:

0.00

AC:

AN:

57706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3068

European-Non Finnish (NFE)

AF:

0.00000728

AC:

AN:

412126

Other (OTH)

AF:

0.00

AC:

AN:

26662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000753

AC:

AN:

132774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35968

American (AMR)

AF:

0.00

AC:

AN:

12748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3284

East Asian (EAS)

AF:

0.00

AC:

AN:

4542

South Asian (SAS)

AF:

0.00

AC:

AN:

3992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000161

AC:

AN:

62174

Other (OTH)

AF:

0.00

AC:

AN:

1800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

1013

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-235379947-CAAAAAAAAA-CAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over