1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

Publications

0 publications found

Variant links:

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]

B3GALNT2 links:

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: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
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: G2P, PanelApp Australia, ClinGen, Ambry Genetics
autosomal recessive Kenny-Caffey syndrome
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

TBCE links:

ENSG00000285053 (HGNC:):

ENSG00000285053 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_152490.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

AF XY:

0.0235

AC XY:

5776

AN XY:

245912

show subpopulations

⚠️ 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:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.302

Heterozygous variant carriers

698

1396

2094

2792

3490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.157

AC:

10281

AN:

65310

Hom.:

698

Cov.:

AF XY:

0.154

AC XY:

4696

AN XY:

30422

show subpopulations

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:

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:

AN:

128

European-Non Finnish (NFE)

AF:

0.129

AC:

3898

AN:

30200

Other (OTH)

AF:

0.157

AC:

136

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

408

817

1225

1634

2042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00604

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over