1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

Variant summary

Our verdict is . The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152490.5(B3GALNT2):c.*1983_*1985delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 519,134 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0071 ( 0 hom. )

Consequence

B3GALNT2
NM_152490.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0510

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Variant has high frequency in the EAS (0.0082) population. However there is too low homozygotes in high coverage region: (expected more than 4, got 0).

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_1985delTTT	3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
TBCE	NM_003193.5	MANE Select	c.1400-111_1400-109delAAA	intron	N/A	NP_003184.1	Q15813-1
TBCE	NM_001287801.2		c.1553-111_1553-109delAAA	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_1985delTTT	3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
TBCE	ENST00000642610.2	MANE Select	c.1400-111_1400-109delAAA	intron	N/A	ENSP00000494796.1	Q15813-1
ENSG00000285053	ENST00000647186.1		c.1400-111_1400-109delAAA	intron	N/A	ENSP00000494775.1

Frequencies

GnomAD3 genomes

AF:

0.0000915

AC:

AN:

65580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000192

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000806

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00706

AC:

3200

AN:

453554

Hom.:

AF XY:

0.00684

AC XY:

1681

AN XY:

245888

show subpopulations

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

African (AFR)

AF:

0.00523

AC:

AN:

11098

American (AMR)

AF:

0.00600

AC:

142

AN:

23670

Ashkenazi Jewish (ASJ)

AF:

0.00860

AC:

129

AN:

15002

East Asian (EAS)

AF:

0.00913

AC:

250

AN:

27378

South Asian (SAS)

AF:

0.00218

AC:

112

AN:

51260

European-Finnish (FIN)

AF:

0.00910

AC:

261

AN:

28676

Middle Eastern (MID)

AF:

0.00377

AC:

AN:

2920

European-Non Finnish (NFE)

AF:

0.00763

AC:

2053

AN:

269230

Other (OTH)

AF:

0.00757

AC:

184

AN:

24320

⚠️ 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: 0.259

Heterozygous variant carriers

384

769

1153

1538

1922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.0000915

AC:

AN:

65580

Hom.:

Cov.:

AF XY:

0.0000982

AC XY:

AN XY:

30556

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

20884

American (AMR)

AF:

0.00

AC:

AN:

5664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1636

East Asian (EAS)

AF:

0.00

AC:

AN:

1664

South Asian (SAS)

AF:

0.00

AC:

AN:

1594

European-Finnish (FIN)

AF:

0.000806

AC:

AN:

2480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

30296

Other (OTH)

AF:

0.00

AC:

AN:

860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.051

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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