1-235448220-C-CAAA

Position:

• chr1-235448220-C-CAAA

Variant summary

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

The NM_152490.5(B3GALNT2):​c.*1985_*1986insTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 519,164 control chromosomes in the GnomAD database, including 701 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (698 hom., cov: 24)
  • Exomes 𝑓: 0.023 (3 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-235448220-C-CAAA is Benign according to our data. Variant chr1-235448220-C-CAAA is described in ClinVar as [Benign]. Clinvar id is 1233617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALNT2	NM_152490.5	c.*1985_*1986insTTT		3_prime_UTR_variant	12/12	ENST00000366600.8
TBCE	NM_003193.5	c.1400-111_1400-109dup		intron_variant		ENST00000642610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.*1985_*1986insTTT		3_prime_UTR_variant	12/12	1	NM_152490.5	P1
TBCE	ENST00000642610.2	c.1400-111_1400-109dup		intron_variant			NM_003193.5	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 10281 AN: 65294 Hom.: 698 Cov.: 24

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0414

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.0234 AC: 10608 AN: 453854 Hom.: 3 AF XY: 0.0235 AC XY: 5776 AN XY: 245912

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.0157

Gnomad4 ASJ exome AF: 0.0225

Gnomad4 EAS exome AF: 0.00610

Gnomad4 SAS exome AF: 0.0285

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0270

GnomAD4 genome AF: 0.157 AC: 10281 AN: 65310 Hom.: 698 Cov.: 24 AF XY: 0.154 AC XY: 4696 AN XY: 30422

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.157

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

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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;