1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chr1-235448220-C-CAAA
• rs59405398
• NM_152490.5:c.*1983_*1985dupTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_152490.5(B3GALNT2):​c.*1983_*1985dupTTT 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
• Publications: 0 publications found

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]

TBCE Gene-Disease associations (from GenCC):

• hypoparathyroidism-retardation-dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• encephalopathy, progressive, with amyotrophy and optic atrophy

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen, G2P, Ambry Genetics
• autosomal recessive Kenny-Caffey syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ENSG00000285053 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152490.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	NM_152490.5	MANE Select	c.*1983_*1985dupTTT		3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
	TBCE	NM_003193.5	MANE Select	c.1400-111_1400-109dupAAA		intron	N/A	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.1553-111_1553-109dupAAA		intron	N/A	NP_001274730.1	Q15813-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.*1983_*1985dupTTT		3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
	TBCE	ENST00000642610.2	MANE Select	c.1400-111_1400-109dupAAA		intron	N/A	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.1400-111_1400-109dupAAA		intron	N/A	ENSP00000494775.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0833 AC: 876 AN: 10510

American (AMR) AF: 0.0157 AC: 375 AN: 23860

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 337 AN: 14974

East Asian (EAS) AF: 0.00610 AC: 171 AN: 28034

South Asian (SAS) AF: 0.0285 AC: 1446 AN: 50744

European-Finnish (FIN) AF: 0.0121 AC: 351 AN: 29114

Middle Eastern (MID) AF: 0.0157 AC: 46 AN: 2938

European-Non Finnish (NFE) AF: 0.0236 AC: 6350 AN: 269350

Other (OTH) AF: 0.0270 AC: 656 AN: 24330

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.248 AC: 5157 AN: 20766

American (AMR) AF: 0.0938 AC: 530 AN: 5652

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 197 AN: 1630

East Asian (EAS) AF: 0.0301 AC: 50 AN: 1660

South Asian (SAS) AF: 0.111 AC: 174 AN: 1570

European-Finnish (FIN) AF: 0.0408 AC: 101 AN: 2474

Middle Eastern (MID) AF: 0.180 AC: 23 AN: 128

European-Non Finnish (NFE) AF: 0.129 AC: 3898 AN: 30200

Other (OTH) AF: 0.157 AC: 136 AN: 868

Alfa AF: 0.00604 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs59405398; hg19: chr1-235611535;