Genetic Variant TBCE:c.100+54_100+65dupGTGTGTGTGTGT (chr1-235380161-T-TTGTGTGTGTGTG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003193.5(TBCE):c.100+54_100+65dupGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBCE
NM_003193.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.401

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), G2P, Orphanet
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, LIMITED Submitted by: Ambry Genetics, G2P
autosomal recessive Kenny-Caffey syndrome
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

TBCE links:

ENSG00000285053 (HGNC:):

ENSG00000285053 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5 link	c.100+54_100+65dupGTGTGTGTGTGT	intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1	Q15813-1
TBCE	NM_001287801.2 link	c.100+54_100+65dupGTGTGTGTGTGT	intron_variant	Intron 2 of 17		NP_001274730.1	Q15813-2
TBCE	NM_001079515.3 link	c.100+54_100+65dupGTGTGTGTGTGT	intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2 link	c.-211+54_-211+65dupGTGTGTGTGTGT	intron_variant	Intron 2 of 15		NP_001274731.1	Q15813A0A2R8Y6Q1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2 link	c.100+12_100+13insTGTGTGTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1		Q15813-1
ENSG00000285053	ENST00000647186.1 link	c.100+12_100+13insTGTGTGTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1		Q15813-1

Frequencies

GnomAD3 genomes

AF:

0.0000143

AC:

AN:

139844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000740

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:

0.0000155

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

998914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

512076

African (AFR)

AF:

0.00

AC:

AN:

25168

American (AMR)

AF:

0.00

AC:

AN:

41600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21144

East Asian (EAS)

AF:

0.00

AC:

AN:

34036

South Asian (SAS)

AF:

0.00

AC:

AN:

74840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4514

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

707726

Other (OTH)

AF:

0.00

AC:

AN:

43370

GnomAD4 genome

AF:

0.0000143

AC:

AN:

139844

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

67006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38248

American (AMR)

AF:

0.0000740

AC:

AN:

13508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3314

East Asian (EAS)

AF:

0.00

AC:

AN:

4758

South Asian (SAS)

AF:

0.00

AC:

AN:

4090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

64516

Other (OTH)

AF:

0.00

AC:

AN:

1882

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

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over