1-235448220-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

Variant summary

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

The NM_152490.5(B3GALNT2):c.*1984_*1985dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 520,352 control chromosomes in the GnomAD database, including 120 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.047 ( 119 hom., cov: 24)

Exomes 𝑓: 0.018 ( 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-C-CAA is Benign according to our data. Variant chr1-235448220-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1250633.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0877 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.1984_1985dupTT	3_prime_UTR	Exon 12 of 12	NP_689703.1	Q8NCR0-1
TBCE	NM_003193.5	MANE Select	c.1400-110_1400-109dupAA	intron	N/A	NP_003184.1	Q15813-1
TBCE	NM_001287801.2		c.1553-110_1553-109dupAA	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_1985dupTT	3_prime_UTR	Exon 12 of 12	ENSP00000355559.3	Q8NCR0-1
TBCE	ENST00000642610.2	MANE Select	c.1400-110_1400-109dupAA	intron	N/A	ENSP00000494796.1	Q15813-1
ENSG00000285053	ENST00000647186.1		c.1400-110_1400-109dupAA	intron	N/A	ENSP00000494775.1

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

3076

AN:

65468

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0909

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.0777

Gnomad EAS

AF:

0.000602

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00362

Gnomad MID

AF:

0.0725

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0385

GnomAD4 exome

AF:

0.0178

AC:

8117

AN:

454866

Hom.:

AF XY:

0.0176

AC XY:

4331

AN XY:

246624

show subpopulations

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

African (AFR)

AF:

0.0611

AC:

661

AN:

10816

American (AMR)

AF:

0.0137

AC:

326

AN:

23846

Ashkenazi Jewish (ASJ)

AF:

0.0273

AC:

409

AN:

14978

East Asian (EAS)

AF:

0.00921

AC:

256

AN:

27786

South Asian (SAS)

AF:

0.0128

AC:

656

AN:

51158

European-Finnish (FIN)

AF:

0.00885

AC:

257

AN:

29050

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

2908

European-Non Finnish (NFE)

AF:

0.0184

AC:

4972

AN:

269950

Other (OTH)

AF:

0.0220

AC:

536

AN:

24374

⚠️ 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: 0.283

Heterozygous variant carriers

767

1534

2300

3067

3834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<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:

0.0470

AC:

3080

AN:

65486

Hom.:

119

Cov.:

AF XY:

0.0463

AC XY:

1415

AN XY:

30540

show subpopulations

African (AFR)

AF:

0.0911

AC:

1902

AN:

20876

American (AMR)

AF:

0.0259

AC:

147

AN:

5674

Ashkenazi Jewish (ASJ)

AF:

0.0777

AC:

127

AN:

1634

East Asian (EAS)

AF:

0.000602

AC:

AN:

1660

South Asian (SAS)

AF:

0.0165

AC:

AN:

1580

European-Finnish (FIN)

AF:

0.00362

AC:

AN:

2484

Middle Eastern (MID)

AF:

0.0794

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.0273

AC:

825

AN:

30224

Other (OTH)

AF:

0.0380

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

127

253

380

506

633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00192

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

(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