1-235448220-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chr1-235448220-C-CAAAAA
• rs59405398
• NM_152490.5:c.*1981_*1985dupTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_152490.5(B3GALNT2):​c.*1981_*1985dupTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 530,564 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 0.00049 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00045 (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000445 (207/465066) while in subpopulation AFR AF= 0.00232 (26/11218). AF 95% confidence interval is 0.00162. There are 0 homozygotes in gnomad4_exome. There are 110 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.*1981_*1985dupTTTTT		3_prime_UTR_variant	Exon 12 of 12	ENST00000366600.8	NP_689703.1
TBCE	NM_003193.5	c.1400-113_1400-109dupAAAAA		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.*1981_*1985dupTTTTT		3_prime_UTR_variant	Exon 12 of 12	1	NM_152490.5	ENSP00000355559.3
TBCE	ENST00000642610.2	c.1400-113_1400-109dupAAAAA		intron_variant	Intron 15 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000645655.1	c.1400-113_1400-109dupAAAAA		intron_variant	Intron 18 of 19			ENSP00000495202.1

Frequencies

GnomAD3 genomes AF: 0.000489 AC: 32 AN: 65480 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000624

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000630

Gnomad FIN AF: 0.000403

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000430

Gnomad OTH AF: 0.00117

GnomAD4 exome AF: 0.000445 AC: 207 AN: 465066 Hom.: 0 AF XY: 0.000436 AC XY: 110 AN XY: 252054

Gnomad4 AFR exome AF: 0.00232

Gnomad4 AMR exome AF: 0.000165

Gnomad4 ASJ exome AF: 0.000586

Gnomad4 EAS exome AF: 0.0000708

Gnomad4 SAS exome AF: 0.000457

Gnomad4 FIN exome AF: 0.0000678

Gnomad4 NFE exome AF: 0.000456

Gnomad4 OTH exome AF: 0.000561

GnomAD4 genome AF: 0.000489 AC: 32 AN: 65498 Hom.: 0 Cov.: 24 AF XY: 0.000491 AC XY: 15 AN XY: 30530

Gnomad4 AFR AF: 0.000624

Gnomad4 AMR AF: 0.000529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000634

Gnomad4 FIN AF: 0.000403

Gnomad4 NFE AF: 0.000429

Gnomad4 OTH AF: 0.00115

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;