1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr1-235380161-T-TTGTGTG
• rs10524346
• NM_003193.5:c.100+60_100+65dupGTGTGT

Variant summary

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

The NM_003193.5(TBCE):​c.100+60_100+65dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.100+60_100+65dupGTGTGT		intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.100+60_100+65dupGTGTGT		intron_variant	Intron 2 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.100+60_100+65dupGTGTGT		intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-211+60_-211+65dupGTGTGT		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+12_100+13insTGTGTG		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000647186.1	c.100+12_100+13insTGTGTG		intron_variant	Intron 4 of 18			ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.000279 AC: 39 AN: 139842 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000370

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000120

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000372

Gnomad OTH AF: 0.00106

GnomAD4 exome AF: 0.0000471 AC: 47 AN: 998896 Hom.: 0 Cov.: 0 AF XY: 0.0000488 AC XY: 25 AN XY: 512064

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

African (AFR) AF: 0.0000397 AC: 1 AN: 25168

American (AMR) AF: 0.0000240 AC: 1 AN: 41600

Ashkenazi Jewish (ASJ) AF: 0.0000473 AC: 1 AN: 21144

East Asian (EAS) AF: 0.000206 AC: 7 AN: 34032

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4514

European-Non Finnish (NFE) AF: 0.0000480 AC: 34 AN: 707714

Other (OTH) AF: 0.0000461 AC: 2 AN: 43368

⚠️ 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.

GnomAD4 genome AF: 0.000279 AC: 39 AN: 139842 Hom.: 0 Cov.: 0 AF XY: 0.000254 AC XY: 17 AN XY: 67006

African (AFR) AF: 0.000183 AC: 7 AN: 38248

American (AMR) AF: 0.000370 AC: 5 AN: 13506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3314

East Asian (EAS) AF: 0.00 AC: 0 AN: 4758

South Asian (SAS) AF: 0.00 AC: 0 AN: 4090

European-Finnish (FIN) AF: 0.000120 AC: 1 AN: 8350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.000372 AC: 24 AN: 64516

Other (OTH) AF: 0.00106 AC: 2 AN: 1882

Alfa AF: 0.00 Hom.: 546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism

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;