1-235436814-T-C

Variant names:

• chr1-235436814-T-C
• rs6429082
• NM_003193.5:c.963+206T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003193.5(TBCE):​c.963+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,986 control chromosomes in the GnomAD database, including 23,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (23163 hom., cov: 33)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.34
• Publications: 22 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 1-235436814-T-C is Benign according to our data. Variant chr1-235436814-T-C is described in ClinVar as Benign. ClinVar VariationId is 1251326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003193.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCE	NM_003193.5	MANE Select	c.963+206T>C		intron	N/A	NP_003184.1
	TBCE	NM_001287801.2		c.1116+206T>C		intron	N/A	NP_001274730.1
	TBCE	NM_001079515.3		c.963+206T>C		intron	N/A	NP_001072983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCE	ENST00000642610.2	MANE Select	c.963+206T>C		intron	N/A	ENSP00000494796.1
	ENSG00000285053	ENST00000647186.1		c.963+206T>C		intron	N/A	ENSP00000494775.1
	TBCE	ENST00000366601.8	TSL:1	c.774+206T>C		intron	N/A	ENSP00000355560.4

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83471 AN: 151868 Hom.: 23129 Cov.: 33

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.558

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 83572 AN: 151986 Hom.: 23163 Cov.: 33 AF XY: 0.551 AC XY: 40928 AN XY: 74270

African (AFR) AF: 0.545 AC: 22602 AN: 41448

American (AMR) AF: 0.603 AC: 9201 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1907 AN: 3472

East Asian (EAS) AF: 0.653 AC: 3368 AN: 5158

South Asian (SAS) AF: 0.483 AC: 2329 AN: 4822

European-Finnish (FIN) AF: 0.570 AC: 6000 AN: 10530

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36241 AN: 67976

Other (OTH) AF: 0.563 AC: 1185 AN: 2106

Alfa AF: 0.540 Hom.: 64292

Bravo AF: 0.556

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.019
DANN	Benign	0.25
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6429082; hg19: chr1-235600129;