rs1416473

Variant names:

• chr1-235399944-C-T
• rs1416473
• NM_003193.5:c.101-1559C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003193.5(TBCE):​c.101-1559C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,046 control chromosomes in the GnomAD database, including 42,091 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (42091 hom., cov: 31)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.101-1559C>T		intron_variant	Intron 2 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.101-1559C>T		intron_variant	Intron 2 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.101-1559C>T		intron_variant	Intron 2 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-210-14489C>T		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.101-1559C>T		intron_variant	Intron 2 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000647186.1	c.101-1559C>T		intron_variant	Intron 4 of 18			ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111373 AN: 151928 Hom.: 42023 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.733 AC: 111510 AN: 152046 Hom.: 42091 Cov.: 31 AF XY: 0.731 AC XY: 54308 AN XY: 74308

African (AFR) AF: 0.925 AC: 38405 AN: 41528

American (AMR) AF: 0.687 AC: 10482 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3441 AN: 5158

South Asian (SAS) AF: 0.565 AC: 2721 AN: 4816

European-Finnish (FIN) AF: 0.683 AC: 7219 AN: 10562

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.653 AC: 44397 AN: 67948

Other (OTH) AF: 0.741 AC: 1563 AN: 2110

Alfa AF: 0.535 Hom.: 1142

Bravo AF: 0.745

Asia WGS AF: 0.645 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.37
PhyloP100		-1.0
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: rs1416473; hg19: chr1-235563259; COSMIC: COSV64005526; COSMIC: COSV64005526;