1-235450264-G-C

Variant names:

• chr1-235450264-G-C
• rs541697587
• NM_152490.5:c.1445C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000366600.8(B3GALNT2):​c.1445C>G​(p.Thr482Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T482M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GALNT2 ENST00000366600.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044790924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366600.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	NM_152490.5	MANE Select	c.1445C>G	p.Thr482Arg	missense	Exon 12 of 12	NP_689703.1
	TBCE	NM_003193.5	MANE Select	c.*1502G>C		3_prime_UTR	Exon 17 of 17	NP_003184.1
	TBCE	NM_001287801.2		c.*1502G>C		3_prime_UTR	Exon 18 of 18	NP_001274730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.1445C>G	p.Thr482Arg	missense	Exon 12 of 12	ENSP00000355559.3
	TBCE	ENST00000642610.2	MANE Select	c.*1502G>C		3_prime_UTR	Exon 17 of 17	ENSP00000494796.1
	B3GALNT2	ENST00000675555.1		c.1223C>G	p.Thr408Arg	missense	Exon 12 of 12	ENSP00000501896.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.21
DANN	Benign	0.71
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.041
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.066
Sift	Benign	0.70	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.43		Gain of MoRF binding (P = 0.0151)
MVP		0.29
MPC		0.28
ClinPred		0.021	T
GERP RS		1.1
Varity_R		0.033
gMVP		0.70
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs541697587; hg19: chr1-235613579;