rs10524346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_003193.5(TBCE):c.100+24_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000001 in 998,910 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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: not found (cov: 0)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

TBCE
NM_003193.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.667

Publications

0 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+24_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT	intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1	Q15813-1
TBCE	NM_001287801.2 link	c.100+24_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT	intron_variant	Intron 2 of 17		NP_001274730.1	Q15813-2
TBCE	NM_001079515.3 link	c.100+24_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT	intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2 link	c.-211+24_-211+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT	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+13_100+54delTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1		Q15813-1
ENSG00000285053	ENST00000647186.1 link	c.100+13_100+54delTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1		Q15813-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000100

AC:

AN:

998910

Hom.:

AF XY:

0.00000195

AC XY:

AN XY:

512076

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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:

0.00000141

AC:

AN:

707722

Other (OTH)

AF:

0.00

AC:

AN:

43370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.67

Splicing

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

Publications

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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