1-235379947-C-CA

Variant names:

• chr1-235379947-C-CA
• rs36068852
• NM_003193.5:c.-31-55dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003193.5(TBCE):​c.-31-55dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (34119 hom., cov: 0)
  • Exomes 𝑓: 0.41 (1954 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.566
• 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), PanelApp Australia, Orphanet, G2P
• 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, MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen, G2P, Ambry Genetics
• autosomal recessive Kenny-Caffey syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ENSG00000285053 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-235379947-C-CA is Benign according to our data. Variant chr1-235379947-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1174300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCE	NM_003193.5	MANE Select	c.-31-55dupA		intron	N/A	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.-31-55dupA		intron	N/A	NP_001274730.1	Q15813-2
	TBCE	NM_001079515.3		c.-31-55dupA		intron	N/A	NP_001072983.1	Q15813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCE	ENST00000642610.2	MANE Select	c.-31-72_-31-71insA		intron	N/A	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.-31-72_-31-71insA		intron	N/A	ENSP00000494775.1
	TBCE	ENST00000366601.8	TSL:1	c.-31-72_-31-71insA		intron	N/A	ENSP00000355560.4	A0A2U3TZJ6

Frequencies

GnomAD3 genomes AF: 0.721 AC: 95665 AN: 132642 Hom.: 34104 Cov.: 0

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.728

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.405 AC: 239520 AN: 590892 Hom.: 1954 AF XY: 0.404 AC XY: 125428 AN XY: 310450

African (AFR) AF: 0.457 AC: 5826 AN: 12748

American (AMR) AF: 0.397 AC: 9794 AN: 24668

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 5851 AN: 14006

East Asian (EAS) AF: 0.395 AC: 8234 AN: 20822

South Asian (SAS) AF: 0.380 AC: 21547 AN: 56658

European-Finnish (FIN) AF: 0.406 AC: 9583 AN: 23600

Middle Eastern (MID) AF: 0.413 AC: 1261 AN: 3054

European-Non Finnish (NFE) AF: 0.407 AC: 166541 AN: 408944

Other (OTH) AF: 0.412 AC: 10883 AN: 26392

GnomAD4 genome AF: 0.721 AC: 95703 AN: 132672 Hom.: 34119 Cov.: 0 AF XY: 0.719 AC XY: 45339 AN XY: 63072

African (AFR) AF: 0.860 AC: 30986 AN: 36012

American (AMR) AF: 0.693 AC: 8840 AN: 12760

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2322 AN: 3278

East Asian (EAS) AF: 0.648 AC: 2931 AN: 4522

South Asian (SAS) AF: 0.589 AC: 2335 AN: 3966

European-Finnish (FIN) AF: 0.650 AC: 4646 AN: 7146

Middle Eastern (MID) AF: 0.720 AC: 190 AN: 264

European-Non Finnish (NFE) AF: 0.669 AC: 41522 AN: 62078

Other (OTH) AF: 0.729 AC: 1321 AN: 1812

Alfa AF: 0.527 Hom.: 1013

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57
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: rs36068852; hg19: chr1-235543262;