1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

Variant summary

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

The NM_152490.5(B3GALNT2):c.*1985delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 506,400 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.062 ( 45 hom., cov: 24)

Exomes 𝑓: 0.19 ( 1 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-CA-C is Benign according to our data. Variant chr1-235448220-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1242668.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 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.*1985delT	3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
TBCE	NM_003193.5	MANE Select	c.1400-109delA	intron	N/A	NP_003184.1	Q15813-1
TBCE	NM_001287801.2		c.1553-109delA	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.*1985delT	3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
TBCE	ENST00000642610.2	MANE Select	c.1400-109delA	intron	N/A	ENSP00000494796.1	Q15813-1
ENSG00000285053	ENST00000647186.1		c.1400-109delA	intron	N/A	ENSP00000494775.1

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

4038

AN:

65546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0417

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.0339

Gnomad FIN

AF:

0.0842

Gnomad MID

AF:

0.0362

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.0500

GnomAD4 exome

AF:

0.192

AC:

84760

AN:

440836

Hom.:

AF XY:

0.190

AC XY:

45393

AN XY:

238636

show subpopulations

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

African (AFR)

AF:

0.144

AC:

1538

AN:

10714

American (AMR)

AF:

0.189

AC:

4299

AN:

22702

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

2512

AN:

14734

East Asian (EAS)

AF:

0.234

AC:

6248

AN:

26686

South Asian (SAS)

AF:

0.166

AC:

8063

AN:

48582

European-Finnish (FIN)

AF:

0.203

AC:

5726

AN:

28274

Middle Eastern (MID)

AF:

0.136

AC:

390

AN:

2870

European-Non Finnish (NFE)

AF:

0.195

AC:

51227

AN:

262438

Other (OTH)

AF:

0.200

AC:

4757

AN:

23836

⚠️ 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: 0.310

Heterozygous variant carriers

5563

11126

16689

22252

27815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

400

800

1200

1600

2000

<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:

0.0616

AC:

4038

AN:

65564

Hom.:

Cov.:

AF XY:

0.0632

AC XY:

1932

AN XY:

30564

show subpopulations

African (AFR)

AF:

0.0828

AC:

1729

AN:

20874

American (AMR)

AF:

0.0416

AC:

236

AN:

5672

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

AN:

1634

East Asian (EAS)

AF:

0.0150

AC:

AN:

1664

South Asian (SAS)

AF:

0.0341

AC:

AN:

1584

European-Finnish (FIN)

AF:

0.0842

AC:

209

AN:

2482

Middle Eastern (MID)

AF:

0.0397

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.0535

AC:

1620

AN:

30294

Other (OTH)

AF:

0.0494

AC:

AN:

870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

142

283

425

566

708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.00879

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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