Genetic Variant NM_054025.3:c.608A>C (chr11-134383693-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_054025.3(B3GAT1):c.608A>C(p.Glu203Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,580,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

B3GAT1
NM_054025.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

Publications

0 publications found

Variant links:

Genes affected

B3GAT1 (HGNC:921): (beta-1,3-glucuronyltransferase 1) The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

B3GAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT1	NM_054025.3 link	c.608A>C	p.Glu203Ala	missense_variant	Exon 3 of 6	ENST00000312527.9	NP_473366.1	Q9P2W7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
B3GAT1	ENST00000312527.9 link	c.608A>C	p.Glu203Ala	missense_variant	Exon 3 of 6	1	NM_054025.3	ENSP00000307875.4	Q9P2W7-1
B3GAT1	ENST00000392580.5 link	c.608A>C	p.Glu203Ala	missense_variant	Exon 4 of 7	1		ENSP00000376359.1	Q9P2W7-1
B3GAT1	ENST00000531778.1 link	n.3505A>C		non_coding_transcript_exon_variant	Exon 1 of 4	1
B3GAT1	ENST00000524765.1 link	c.608A>C	p.Glu203Ala	missense_variant	Exon 3 of 6	2		ENSP00000433847.1	Q9P2W7-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000132

AC:

AN:

227188

AF XY:

0.0000162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000296

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1428568

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

705028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32822

American (AMR)

AF:

0.00

AC:

AN:

42586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24866

East Asian (EAS)

AF:

0.00

AC:

AN:

38876

South Asian (SAS)

AF:

0.00

AC:

AN:

82618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.0000358

AC:

AN:

1090794

Other (OTH)

AF:

0.00

AC:

AN:

58796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 16, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.608A>C (p.E203A) alteration is located in exon 3 (coding exon 2) of the B3GAT1 gene. This alteration results from a A to C substitution at nucleotide position 608, causing the glutamic acid (E) at amino acid position 203 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;D;D

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;.;.

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.5

M;M;M

PhyloP100

8.0

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.14

B;B;B

Vest4

0.86

MVP

0.35

MPC

1.7

ClinPred

0.93

GERP RS

5.7

Varity_R

0.77

gMVP

0.92

Mutation Taster

=19/81

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_054025.3:c.608A>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over