1-235450253-TCCACAGTTCCGTCAGTTC-TCCACAGTTCCGTCAGTTCCCACAGTTCCGTCAGTTC

Variant names:

• chr1-235450253-T-TCCACAGTTCCGTCAGTTC
• rs863224849
• NM_152490.5:c.1438_1455dupGAACTGACGGAACTGTGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_152490.5(B3GALNT2):​c.1438_1455dupGAACTGACGGAACTGTGG​(p.Trp485_Lys486insGluLeuThrGluLeuTrp) variant causes a conservative inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GALNT2 NM_152490.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• 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), 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_152490.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.1438_1455dupGAACTGACGGAACTGTGG	p.Trp485_Lys486insGluLeuThrGluLeuTrp	conservative_inframe_insertion	Exon 12 of 12	ENST00000366600.8	NP_689703.1
TBCE	NM_003193.5	c.*1496_*1513dupAGTTCCGTCAGTTCCCAC		3_prime_UTR_variant	Exon 17 of 17	ENST00000642610.2	NP_003184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.1438_1455dupGAACTGACGGAACTGTGG	p.Trp485_Lys486insGluLeuThrGluLeuTrp	conservative_inframe_insertion	Exon 12 of 12	1	NM_152490.5	ENSP00000355559.3
TBCE	ENST00000642610.2	c.*1496_*1513dupAGTTCCGTCAGTTCCCAC		3_prime_UTR_variant	Exon 17 of 17		NM_003193.5	ENSP00000494796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2
Mutation Taster		=68/32	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs863224849; hg19: chr1-235613568;