1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAAA

Variant names:

Variant summary

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

The NM_152490.5(B3GALNT2):c.*1984_*1985delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 500,738 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 0.00015 ( 0 hom., cov: 24)

Exomes 𝑓: 0.037 ( 0 hom. )

Consequence

B3GALNT2
NM_152490.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.103

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 (0.0443) population. However there is too low homozygotes in high coverage region: (expected more than 126, 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.1984_1985delTT	3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
TBCE	NM_003193.5	MANE Select	c.1400-110_1400-109delAA	intron	N/A	NP_003184.1	Q15813-1
TBCE	NM_001287801.2		c.1553-110_1553-109delAA	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.1984_1985delTT	3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
TBCE	ENST00000642610.2	MANE Select	c.1400-110_1400-109delAA	intron	N/A	ENSP00000494796.1	Q15813-1
ENSG00000285053	ENST00000647186.1		c.1400-110_1400-109delAA	intron	N/A	ENSP00000494775.1

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

65582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000479

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:

0.00121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000198

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0366

AC:

15935

AN:

435156

Hom.:

AF XY:

0.0358

AC XY:

8443

AN XY:

235854

show subpopulations

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

African (AFR)

AF:

0.0304

AC:

328

AN:

10796

American (AMR)

AF:

0.0316

AC:

707

AN:

22406

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

547

AN:

14580

East Asian (EAS)

AF:

0.0465

AC:

1218

AN:

26182

South Asian (SAS)

AF:

0.0175

AC:

848

AN:

48346

European-Finnish (FIN)

AF:

0.0453

AC:

1255

AN:

27684

Middle Eastern (MID)

AF:

0.0358

AC:

102

AN:

2848

European-Non Finnish (NFE)

AF:

0.0386

AC:

9993

AN:

258930

Other (OTH)

AF:

0.0401

AC:

937

AN:

23384

⚠️ 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: 0.273

Heterozygous variant carriers

1541

3081

4622

6162

7703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

140

210

280

350

<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:

0.000152

AC:

AN:

65582

Hom.:

Cov.:

AF XY:

0.0000982

AC XY:

AN XY:

30554

show subpopulations

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

African (AFR)

AF:

0.0000479

AC:

AN:

20882

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:

0.00121

AC:

AN:

2484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.000198

AC:

AN:

30296

Other (OTH)

AF:

0.00

AC:

AN:

860

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000710211), 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

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:

0.000206

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.10

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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