1-235448220-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chr1-235448220-C-CAAAA
• rs59405398
• NM_152490.5:c.*1982_*1985dupTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_152490.5(B3GALNT2):​c.*1982_*1985dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 462,840 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (6 hom., cov: 24)
  • Exomes 𝑓: 0.0048 (4 hom.)
  • Failed GnomAD Quality Control
• 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00479 (2219/462840) while in subpopulation AFR AF= 0.0247 (273/11034). AF 95% confidence interval is 0.0223. There are 4 homozygotes in gnomad4_exome. There are 1227 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.*1982_*1985dupTTTT		3_prime_UTR_variant	Exon 12 of 12	ENST00000366600.8	NP_689703.1
TBCE	NM_003193.5	c.1400-112_1400-109dupAAAA		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.*1982_*1985dupTTTT		3_prime_UTR_variant	Exon 12 of 12	1	NM_152490.5	ENSP00000355559.3
TBCE	ENST00000642610.2	c.1400-112_1400-109dupAAAA		intron_variant	Intron 15 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000645655.1	c.1400-112_1400-109dupAAAA		intron_variant	Intron 18 of 19			ENSP00000495202.1

Frequencies

GnomAD3 genomes AF: 0.00461 AC: 302 AN: 65514 Hom.: 6 Cov.: 24

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00275

Gnomad AMR AF: 0.00318

Gnomad ASJ AF: 0.00183

Gnomad EAS AF: 0.000601

Gnomad SAS AF: 0.00314

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00583

GnomAD4 exome AF: 0.00479 AC: 2219 AN: 462840 Hom.: 4 AF XY: 0.00489 AC XY: 1227 AN XY: 250890

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.00306

Gnomad4 ASJ exome AF: 0.00406

Gnomad4 EAS exome AF: 0.000744

Gnomad4 SAS exome AF: 0.00713

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.00455

Gnomad4 OTH exome AF: 0.00415

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00462 AC: 303 AN: 65532 Hom.: 6 Cov.: 24 AF XY: 0.00455 AC XY: 139 AN XY: 30550

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.00317

Gnomad4 ASJ AF: 0.00183

Gnomad4 EAS AF: 0.000601

Gnomad4 SAS AF: 0.00316

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.00576

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;