NM_003193.5:c.-31-57_-31-55dupAAA

Variant names:

• chr1-235379947-C-CAAA
• rs36068852
• NM_003193.5:c.-31-57_-31-55dupAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_003193.5(TBCE):​c.-31-57_-31-55dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 726,730 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

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]

ENSG00000285053 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000105 (14/132784) while in subpopulation EAS AF= 0.00133 (6/4524). AF 95% confidence interval is 0.000577. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.-31-57_-31-55dupAAA		intron_variant	Intron 1 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.-31-57_-31-55dupAAA		intron_variant	Intron 1 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.-31-57_-31-55dupAAA		intron_variant	Intron 1 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-341-57_-341-55dupAAA		intron_variant	Intron 1 of 15		NP_001274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2	c.-31-72_-31-71insAAA		intron_variant	Intron 1 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000645655.1	c.-31-72_-31-71insAAA		intron_variant	Intron 4 of 19			ENSP00000495202.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 14 AN: 132754 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00132

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000280

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000161

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00339 AC: 2011 AN: 593946 Hom.: 0 AF XY: 0.00330 AC XY: 1031 AN XY: 312272

Gnomad4 AFR exome AF: 0.00710

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.00277

Gnomad4 EAS exome AF: 0.00507

Gnomad4 SAS exome AF: 0.00118

Gnomad4 FIN exome AF: 0.00231

Gnomad4 NFE exome AF: 0.00365

Gnomad4 OTH exome AF: 0.00354

GnomAD4 genome AF: 0.000105 AC: 14 AN: 132784 Hom.: 0 Cov.: 0 AF XY: 0.000111 AC XY: 7 AN XY: 63098

Gnomad4 AFR AF: 0.000139

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00133

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000280

Gnomad4 NFE AF: 0.0000161

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36068852; hg19: chr1-235543262;