Genetic Variant NM_001080438.1:c.598G>A (chr1-33307191-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080438.1(A3GALT2):c.598G>A(p.Val200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 1,544,324 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 64 hom. )

Consequence

A3GALT2
NM_001080438.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.932

Publications

2 publications found

Variant links:

Genes affected

A3GALT2 (HGNC:30005): (alpha 1,3-galactosyltransferase 2) Predicted to enable N-acetyllactosaminide 3-alpha-galactosyltransferase activity and alpha-1,3-galactosyltransferase activity. Predicted to be involved in lipid glycosylation. Predicted to act upstream of or within glycosphingolipid biosynthetic process. Predicted to be located in Golgi cisterna membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

A3GALT2 links:

ENSG00000225313 (HGNC:):

ENSG00000225313 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009167373).

BP6

Variant 1-33307191-C-T is Benign according to our data. Variant chr1-33307191-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2638619.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080438.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	A3GALT2	NM_001080438.1	MANE Select	c.598G>A	p.Val200Met	missense	Exon 5 of 5	NP_001073907.1	U3KPV4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
A3GALT2	ENST00000442999.3	TSL:5 MANE Select	c.598G>A	p.Val200Met	missense	Exon 5 of 5	ENSP00000475261.1	U3KPV4
ENSG00000225313	ENST00000457957.2	TSL:5	n.-180C>T		upstream_gene	N/A
ENSG00000225313	ENST00000588828.1	TSL:5	n.-175C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00542

AC:

824

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00896

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00468

AC:

683

AN:

145904

AF XY:

0.00482

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000671

Gnomad NFE exome

AF:

0.00730

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00787

AC:

10956

AN:

1392220

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

5343

AN XY:

688756

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

29072

American (AMR)

AF:

0.00321

AC:

116

AN:

36118

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

422

AN:

24548

East Asian (EAS)

AF:

0.0000298

AC:

AN:

33580

South Asian (SAS)

AF:

0.00145

AC:

113

AN:

77970

European-Finnish (FIN)

AF:

0.00129

AC:

AN:

46612

Middle Eastern (MID)

AF:

0.00177

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00909

AC:

9824

AN:

1080916

Other (OTH)

AF:

0.00641

AC:

370

AN:

57758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

743

1487

2230

2974

3717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.00542

AC:

824

AN:

152104

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

350

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00169

AC:

AN:

41526

American (AMR)

AF:

0.00425

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00161

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00896

AC:

609

AN:

67942

Other (OTH)

AF:

0.00522

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00627

Hom.:

Bravo

AF:

0.00577

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00124

AC:

ESP6500EA

AF:

0.00857

AC:

ExAC

AF:

0.00344

AC:

402

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Likely 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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.24

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0092

PhyloP100

0.93

PrimateAI

Uncertain

0.71

Sift4G

Uncertain

0.0020

Vest4

0.44

MVP

0.36

MPC

0.57

GERP RS

2.5

Varity_R

0.048

gMVP

0.74

Mutation Taster

=93/7

polymorphism

(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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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