1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_003193.5(TBCE):c.100+56_100+65delGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,137,692 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 0)

Exomes 𝑓: 0.0046 ( 17 hom. )

Consequence

TBCE
NM_003193.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.667

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-235380161-TTGTGTGTGTG-T is Benign according to our data. Variant chr1-235380161-TTGTGTGTGTG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1656193.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00649 (908/139948) while in subpopulation EAS AF = 0.0152 (72/4746). AF 95% confidence interval is 0.0124. There are 7 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5 link	c.100+56_100+65delGTGTGTGTGT	intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1	Q15813-1
TBCE	NM_001287801.2 link	c.100+56_100+65delGTGTGTGTGT	intron_variant	Intron 2 of 17		NP_001274730.1	Q15813-2
TBCE	NM_001079515.3 link	c.100+56_100+65delGTGTGTGTGT	intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2 link	c.-211+56_-211+65delGTGTGTGTGT	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+22delTGTGTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1		Q15813-1
ENSG00000285053	ENST00000647186.1 link	c.100+13_100+22delTGTGTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1		Q15813-1

Frequencies

GnomAD3 genomes

AF:

0.00647

AC:

904

AN:

139826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00503

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0151

Gnomad SAS

AF:

0.00244

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0100

Gnomad NFE

AF:

0.00339

Gnomad OTH

AF:

0.00903

GnomAD4 exome

AF:

0.00462

AC:

4614

AN:

997744

Hom.:

AF XY:

0.00486

AC XY:

2484

AN XY:

511438

show subpopulations

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

African (AFR)

AF:

0.00953

AC:

239

AN:

25090

American (AMR)

AF:

0.00200

AC:

AN:

41564

Ashkenazi Jewish (ASJ)

AF:

0.0154

AC:

325

AN:

21102

East Asian (EAS)

AF:

0.0156

AC:

529

AN:

33906

South Asian (SAS)

AF:

0.00698

AC:

521

AN:

74688

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

46476

Middle Eastern (MID)

AF:

0.00532

AC:

AN:

4508

European-Non Finnish (NFE)

AF:

0.00361

AC:

2551

AN:

707106

Other (OTH)

AF:

0.00598

AC:

259

AN:

43304

⚠️ 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: 0.363

Heterozygous variant carriers

250

500

751

1001

1251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00649

AC:

908

AN:

139948

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

426

AN XY:

67130

show subpopulations

African (AFR)

AF:

0.0111

AC:

427

AN:

38360

American (AMR)

AF:

0.00495

AC:

AN:

13526

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3312

East Asian (EAS)

AF:

0.0152

AC:

AN:

4746

South Asian (SAS)

AF:

0.00220

AC:

AN:

4088

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

8350

Middle Eastern (MID)

AF:

0.00719

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00340

AC:

219

AN:

64504

Other (OTH)

AF:

0.0105

AC:

AN:

1906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

546

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.67

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over