1-235448220-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-235448220-C-CAAAAAA
• rs59405398
• NM_152490.5:c.*1980_*1985dupTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152490.5(B3GALNT2):​c.*1980_*1985dupTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000659 in 530,984 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: B3GALNT2 NM_152490.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.*1980_*1985dupTTTTTT		3_prime_UTR_variant	Exon 12 of 12	ENST00000366600.8	NP_689703.1
TBCE	NM_003193.5	c.1400-114_1400-109dupAAAAAA		intron_variant	Intron 15 of 16	ENST00000642610.2	NP_003184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600	c.*1980_*1985dupTTTTTT		3_prime_UTR_variant	Exon 12 of 12	1	NM_152490.5	ENSP00000355559.3
TBCE	ENST00000642610.2	c.1400-114_1400-109dupAAAAAA		intron_variant	Intron 15 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000645655.1	c.1400-114_1400-109dupAAAAAA		intron_variant	Intron 18 of 19			ENSP00000495202.1

Frequencies

GnomAD3 genomes AF: 0.0000610 AC: 4 AN: 65576 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000144

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: 0.0000666 AC: 31 AN: 465390 Hom.: 0 AF XY: 0.0000714 AC XY: 18 AN XY: 252234

Gnomad4 AFR exome AF: 0.000355

Gnomad4 AMR exome AF: 0.0000823

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000761

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000688

Gnomad4 OTH exome AF: 0.0000801

GnomAD4 genome AF: 0.0000610 AC: 4 AN: 65594 Hom.: 0 Cov.: 24 AF XY: 0.0000981 AC XY: 3 AN XY: 30578

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000330

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;