1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-TTGTG

Variant names:

• chr1-235380161-TTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-T
• rs10524346
• NM_003193.5:c.100+28_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003193.5(TBCE):​c.100+28_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,138,750 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• 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, Ambry Genetics, G2P
• autosomal recessive Kenny-Caffey syndrome

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

ENSG00000285053 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.100+28_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron	N/A	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.100+28_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron	N/A	NP_001274730.1	Q15813-2
	TBCE	NM_001079515.3		c.100+28_100+65delGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT		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.100+13_100+50delTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.100+13_100+50delTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000494775.1
	TBCE	ENST00000366601.8	TSL:1	c.100+13_100+50delTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000355560.4	A0A2U3TZJ6

Frequencies

GnomAD3 genomes AF: 0.0000429 AC: 6 AN: 139844 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000930

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000230 AC: 23 AN: 998906 Hom.: 0 AF XY: 0.0000137 AC XY: 7 AN XY: 512070

African (AFR) AF: 0.00 AC: 0 AN: 25168

American (AMR) AF: 0.0000240 AC: 1 AN: 41600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21144

East Asian (EAS) AF: 0.00 AC: 0 AN: 34036

South Asian (SAS) AF: 0.00 AC: 0 AN: 74840

European-Finnish (FIN) AF: 0.0000430 AC: 2 AN: 46516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4514

European-Non Finnish (NFE) AF: 0.0000283 AC: 20 AN: 707718

Other (OTH) AF: 0.00 AC: 0 AN: 43370

GnomAD4 genome AF: 0.0000429 AC: 6 AN: 139844 Hom.: 0 Cov.: 0 AF XY: 0.0000597 AC XY: 4 AN XY: 67006

African (AFR) AF: 0.00 AC: 0 AN: 38248

American (AMR) AF: 0.00 AC: 0 AN: 13508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3314

East Asian (EAS) AF: 0.00 AC: 0 AN: 4758

South Asian (SAS) AF: 0.00 AC: 0 AN: 4090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000930 AC: 6 AN: 64516

Other (OTH) AF: 0.00 AC: 0 AN: 1882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10524346;

hg19: chr1-235543476;