rs6429082

Positions:

• chr1-235436814-T-C
• chr1-235436814-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCE	NM_003193.5	c.963+206T>C		intron_variant		ENST00000642610.2	NP_003184.1
TBCE	NM_001079515.3	c.963+206T>C		intron_variant			NP_001072983.1
TBCE	NM_001287801.2	c.1116+206T>C		intron_variant			NP_001274730.1
TBCE	NM_001287802.2	c.624+206T>C		intron_variant			NP_001274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2	c.963+206T>C		intron_variant			NM_003193.5	ENSP00000494796	P1

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

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.563

Alfa AF: 0.545 Hom.: 30597

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.019
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs6429082; hg19: chr1-235600129;