1-235448220-C-CAA

Position:

• chr1-235448220-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_152490.5(B3GALNT2):​c.*1984_*1985dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 520,352 control chromosomes in the GnomAD database, including 120 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (119 hom., cov: 24)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: B3GALNT2 NM_152490.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.40

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]

ENSG00000285053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-235448220-C-CAA is Benign according to our data. Variant chr1-235448220-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1250633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.*1984_*1985dupTT		3_prime_UTR_variant	12/12	ENST00000366600.8	NP_689703.1
TBCE	NM_003193.5	c.1400-110_1400-109dupAA		intron_variant		ENST00000642610.2	NP_003184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600	c.*1984_*1985dupTT		3_prime_UTR_variant	12/12	1	NM_152490.5	ENSP00000355559.3
TBCE	ENST00000642610.2	c.1400-110_1400-109dupAA		intron_variant			NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000645655.1	c.1400-110_1400-109dupAA		intron_variant				ENSP00000495202.1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 3076 AN: 65468 Hom.: 118 Cov.: 24

Gnomad AFR AF: 0.0909

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0777

Gnomad EAS AF: 0.000602

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00362

Gnomad MID AF: 0.0725

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0385

GnomAD4 exome AF: 0.0178 AC: 8117 AN: 454866 Hom.: 1 AF XY: 0.0176 AC XY: 4331 AN XY: 246624

Gnomad4 AFR exome AF: 0.0611

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.00921

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.00885

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0470 AC: 3080 AN: 65486 Hom.: 119 Cov.: 24 AF XY: 0.0463 AC XY: 1415 AN XY: 30540

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0777

Gnomad4 EAS AF: 0.000602

Gnomad4 SAS AF: 0.0165

Gnomad4 FIN AF: 0.00362

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0380

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59405398; hg19: chr1-235611535;