1-235448220-CAAAAAAAAAAAAAA-CAAA

Variant names:

• chr1-235448220-CAAAAAAAAAAA-C
• rs59405398
• NM_152490.5:c.*1975_*1985delTTTTTTTTTTT

Variant summary

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

The NM_152490.5(B3GALNT2):​c.*1975_*1985delTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 531,016 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 0.000030 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: B3GALNT2 NM_152490.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]

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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152490.5. 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
	B3GALNT2	NM_152490.5	MANE Select	c.*1975_*1985delTTTTTTTTTTT		3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
	TBCE	NM_003193.5	MANE Select	c.1400-119_1400-109delAAAAAAAAAAA		intron	N/A	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.1553-119_1553-109delAAAAAAAAAAA		intron	N/A	NP_001274730.1	Q15813-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.*1975_*1985delTTTTTTTTTTT		3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
	TBCE	ENST00000642610.2	MANE Select	c.1400-119_1400-109delAAAAAAAAAAA		intron	N/A	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.1400-119_1400-109delAAAAAAAAAAA		intron	N/A	ENSP00000494775.1

Frequencies

GnomAD3 genomes AF: 0.0000305 AC: 2 AN: 65586 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000479

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: 0.0000330

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 6 AN: 465430 Hom.: 0 AF XY: 0.0000159 AC XY: 4 AN XY: 252260

African (AFR) AF: 0.00 AC: 0 AN: 11272

American (AMR) AF: 0.00 AC: 0 AN: 24292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15364

East Asian (EAS) AF: 0.00 AC: 0 AN: 28250

South Asian (SAS) AF: 0.00 AC: 0 AN: 52534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2968

European-Non Finnish (NFE) AF: 0.0000217 AC: 6 AN: 276268

Other (OTH) AF: 0.00 AC: 0 AN: 24964

GnomAD4 genome AF: 0.0000305 AC: 2 AN: 65586 Hom.: 0 Cov.: 24 AF XY: 0.0000654 AC XY: 2 AN XY: 30558

African (AFR) AF: 0.0000479 AC: 1 AN: 20884

American (AMR) AF: 0.00 AC: 0 AN: 5664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1636

East Asian (EAS) AF: 0.00 AC: 0 AN: 1664

South Asian (SAS) AF: 0.00 AC: 0 AN: 1594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

European-Non Finnish (NFE) AF: 0.0000330 AC: 1 AN: 30298

Other (OTH) AF: 0.00 AC: 0 AN: 860

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs59405398; hg19: chr1-235611535;