NM_003193.5:c.100+52_100+65delGTGTGTGTGTGTGT

Variant names:

• chr1-235380161-TTGTGTGTGTGTGTG-T
• rs10524346
• NM_003193.5:c.100+52_100+65delGTGTGTGTGTGTGT

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+52_100+65delGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,131,552 control chromosomes in the GnomAD database, including 17,044 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 0.28 (6206 hom., cov: 0)
  • Exomes 𝑓: 0.18 (10838 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-TTGTGTGTGTGTGTG-T is Benign according to our data. Variant chr1-235380161-TTGTGTGTGTGTGTG-T is described in ClinVar as Benign. ClinVar VariationId is 1245486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.100+52_100+65delGTGTGTGTGTGTGT		intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.100+52_100+65delGTGTGTGTGTGTGT		intron_variant	Intron 2 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.100+52_100+65delGTGTGTGTGTGTGT		intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-211+52_-211+65delGTGTGTGTGTGTGT		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+26delTGTGTGTGTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000647186.1	c.100+13_100+26delTGTGTGTGTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 39341 AN: 139648 Hom.: 6200 Cov.: 0

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.157 AC: 27655 AN: 176408 AF XY: 0.157

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.0754

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.183 AC: 181957 AN: 991782 Hom.: 10838 AF XY: 0.184 AC XY: 93366 AN XY: 508320

African (AFR) AF: 0.0904 AC: 2259 AN: 24986

American (AMR) AF: 0.105 AC: 4333 AN: 41226

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 4152 AN: 20952

East Asian (EAS) AF: 0.0767 AC: 2596 AN: 33830

South Asian (SAS) AF: 0.0888 AC: 6596 AN: 74298

European-Finnish (FIN) AF: 0.259 AC: 11921 AN: 45942

Middle Eastern (MID) AF: 0.201 AC: 903 AN: 4482

European-Non Finnish (NFE) AF: 0.201 AC: 141233 AN: 703070

Other (OTH) AF: 0.185 AC: 7964 AN: 42996

GnomAD4 genome AF: 0.282 AC: 39367 AN: 139770 Hom.: 6206 Cov.: 0 AF XY: 0.276 AC XY: 18537 AN XY: 67046

African (AFR) AF: 0.152 AC: 5804 AN: 38296

American (AMR) AF: 0.254 AC: 3434 AN: 13500

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1021 AN: 3314

East Asian (EAS) AF: 0.118 AC: 558 AN: 4742

South Asian (SAS) AF: 0.123 AC: 501 AN: 4082

European-Finnish (FIN) AF: 0.363 AC: 3021 AN: 8324

Middle Eastern (MID) AF: 0.252 AC: 70 AN: 278

European-Non Finnish (NFE) AF: 0.372 AC: 24003 AN: 64458

Other (OTH) AF: 0.302 AC: 574 AN: 1900

Alfa AF: 0.254 Hom.: 546

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 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; COSMIC: COSV106062833;