1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr1-235380161-TTGTGTGTGTGTGTGTGTGTGTG-T
• rs10524346
• NM_003193.5:c.100+44_100+65delGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003193.5(TBCE):​c.100+44_100+65delGTGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 1,137,448 control chromosomes in the GnomAD database, including 3,897 homozygotes. 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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1260 hom., cov: 0)
  • Exomes 𝑓: 0.085 (2637 hom.)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.667
• Publications: 1 publications found

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

ENSG00000285053 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-235380161-TTGTGTGTGTGTGTGTGTGTGTG-T is Benign according to our data. Variant chr1-235380161-TTGTGTGTGTGTGTGTGTGTGTG-T is described in ClinVar as Benign. ClinVar VariationId is 1221862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.100+44_100+65delGTGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.100+44_100+65delGTGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.100+44_100+65delGTGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-211+44_-211+65delGTGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 15		NP_001274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2	c.100+13_100+34delTGTGTGTGTGTGTGTGTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000647186.1	c.100+13_100+34delTGTGTGTGTGTGTGTGTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 17342 AN: 139790 Hom.: 1256 Cov.: 0

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0649

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.0911 AC: 16074 AN: 176408 AF XY: 0.0906

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.0508

Gnomad ASJ exome AF: 0.0848

Gnomad EAS exome AF: 0.0209

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0855

GnomAD4 exome AF: 0.0849 AC: 84680 AN: 997536 Hom.: 2637 AF XY: 0.0855 AC XY: 43697 AN XY: 511306

African (AFR) AF: 0.166 AC: 4163 AN: 25056

American (AMR) AF: 0.0493 AC: 2045 AN: 41446

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 1810 AN: 21122

East Asian (EAS) AF: 0.0192 AC: 650 AN: 33822

South Asian (SAS) AF: 0.0814 AC: 6081 AN: 74686

European-Finnish (FIN) AF: 0.0800 AC: 3716 AN: 46432

Middle Eastern (MID) AF: 0.0965 AC: 435 AN: 4508

European-Non Finnish (NFE) AF: 0.0876 AC: 61935 AN: 707154

Other (OTH) AF: 0.0888 AC: 3845 AN: 43310

GnomAD4 genome AF: 0.124 AC: 17363 AN: 139912 Hom.: 1260 Cov.: 0 AF XY: 0.123 AC XY: 8289 AN XY: 67120

African (AFR) AF: 0.197 AC: 7542 AN: 38342

American (AMR) AF: 0.0875 AC: 1183 AN: 13522

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 317 AN: 3314

East Asian (EAS) AF: 0.0181 AC: 86 AN: 4748

South Asian (SAS) AF: 0.0945 AC: 386 AN: 4086

European-Finnish (FIN) AF: 0.0867 AC: 724 AN: 8346

Middle Eastern (MID) AF: 0.144 AC: 40 AN: 278

European-Non Finnish (NFE) AF: 0.105 AC: 6797 AN: 64492

Other (OTH) AF: 0.121 AC: 231 AN: 1906

Alfa AF: 0.0856 Hom.: 546

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 05, 2019

GeneDx

Significance: 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 (auto)

Splicing

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

Other links and lift over

dbSNP: rs10524346; hg19: chr1-235543476;