1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAA

Variant names:

Variant summary

Our verdict is . The variant received -4 ACMG points: 0P and 4B. BS2

The NM_152490.5(B3GALNT2):c.*1982_*1985dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 462,840 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 24)

Exomes 𝑓: 0.0048 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

B3GALNT2
NM_152490.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

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.1982_1985dupTTTT	3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
TBCE	NM_003193.5	MANE Select	c.1400-112_1400-109dupAAAA	intron	N/A	NP_003184.1	Q15813-1
TBCE	NM_001287801.2		c.1553-112_1553-109dupAAAA	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.1982_1985dupTTTT	3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
TBCE	ENST00000642610.2	MANE Select	c.1400-112_1400-109dupAAAA	intron	N/A	ENSP00000494796.1	Q15813-1
ENSG00000285053	ENST00000647186.1		c.1400-112_1400-109dupAAAA	intron	N/A	ENSP00000494775.1

Frequencies

GnomAD3 genomes

AF:

0.00461

AC:

302

AN:

65514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00275

Gnomad AMR

AF:

0.00318

Gnomad ASJ

AF:

0.00183

Gnomad EAS

AF:

0.000601

Gnomad SAS

AF:

0.00314

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00725

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00583

GnomAD4 exome

AF:

0.00479

AC:

2219

AN:

462840

Hom.:

AF XY:

0.00489

AC XY:

1227

AN XY:

250890

show subpopulations

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

African (AFR)

AF:

0.0247

AC:

273

AN:

11034

American (AMR)

AF:

0.00306

AC:

AN:

24206

Ashkenazi Jewish (ASJ)

AF:

0.00406

AC:

AN:

15264

East Asian (EAS)

AF:

0.000744

AC:

AN:

28216

South Asian (SAS)

AF:

0.00713

AC:

372

AN:

52168

European-Finnish (FIN)

AF:

0.00190

AC:

AN:

29420

Middle Eastern (MID)

AF:

0.00237

AC:

AN:

2956

European-Non Finnish (NFE)

AF:

0.00455

AC:

1251

AN:

274784

Other (OTH)

AF:

0.00415

AC:

103

AN:

24792

⚠️ 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: 0.277

Heterozygous variant carriers

207

413

620

826

1033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00462

AC:

303

AN:

65532

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

139

AN XY:

30550

show subpopulations

African (AFR)

AF:

0.0112

AC:

234

AN:

20858

American (AMR)

AF:

0.00317

AC:

AN:

5672

Ashkenazi Jewish (ASJ)

AF:

0.00183

AC:

AN:

1636

East Asian (EAS)

AF:

0.000601

AC:

AN:

1664

South Asian (SAS)

AF:

0.00316

AC:

AN:

1582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2484

Middle Eastern (MID)

AF:

0.00794

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

30278

Other (OTH)

AF:

0.00576

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00261

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism

(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