1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr1-235380161-TTGTGTGTGTGTGTGTGTGTG-T
• rs10524346
• NM_003193.5:c.100+46_100+65delGTGTGTGTGTGTGTGTGTGT

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+46_100+65delGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,135,084 control chromosomes in the GnomAD database, including 849 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 0.050 (440 hom., cov: 0)
  • Exomes 𝑓: 0.028 (409 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-TTGTGTGTGTGTGTGTGTGTG-T is Benign according to our data. Variant chr1-235380161-TTGTGTGTGTGTGTGTGTGTG-T is described in ClinVar as Benign. ClinVar VariationId is 1259378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.100+46_100+65delGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.100+46_100+65delGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.100+46_100+65delGTGTGTGTGTGTGTGTGTGT		intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-211+46_-211+65delGTGTGTGTGTGTGTGTGTGT		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+32delTGTGTGTGTGTGTGTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000647186.1	c.100+13_100+32delTGTGTGTGTGTGTGTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7017 AN: 139796 Hom.: 439 Cov.: 0

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.00930

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0200

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0461 AC: 8128 AN: 176408 AF XY: 0.0418

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0714

Gnomad ASJ exome AF: 0.0261

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.0181

Gnomad OTH exome AF: 0.0324

GnomAD4 exome AF: 0.0280 AC: 27858 AN: 995172 Hom.: 409 AF XY: 0.0279 AC XY: 14254 AN XY: 510126

African (AFR) AF: 0.130 AC: 3263 AN: 25008

American (AMR) AF: 0.0685 AC: 2817 AN: 41154

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 683 AN: 21076

East Asian (EAS) AF: 0.0939 AC: 3113 AN: 33138

South Asian (SAS) AF: 0.0422 AC: 3133 AN: 74300

European-Finnish (FIN) AF: 0.0277 AC: 1285 AN: 46320

Middle Eastern (MID) AF: 0.0241 AC: 108 AN: 4484

European-Non Finnish (NFE) AF: 0.0170 AC: 12027 AN: 706520

Other (OTH) AF: 0.0331 AC: 1429 AN: 43172

GnomAD4 genome AF: 0.0502 AC: 7019 AN: 139912 Hom.: 440 Cov.: 0 AF XY: 0.0498 AC XY: 3345 AN XY: 67116

African (AFR) AF: 0.141 AC: 5413 AN: 38336

American (AMR) AF: 0.0348 AC: 470 AN: 13520

Ashkenazi Jewish (ASJ) AF: 0.0244 AC: 81 AN: 3314

East Asian (EAS) AF: 0.00696 AC: 33 AN: 4742

South Asian (SAS) AF: 0.00832 AC: 34 AN: 4086

European-Finnish (FIN) AF: 0.0179 AC: 149 AN: 8346

Middle Eastern (MID) AF: 0.0180 AC: 5 AN: 278

European-Non Finnish (NFE) AF: 0.0115 AC: 745 AN: 64508

Other (OTH) AF: 0.0467 AC: 89 AN: 1904

Alfa AF: 0.0226 Hom.: 546

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 06, 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;