Genetic Variant A3GALT2:p.Val200Met (chr1-33307191-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 2638619.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
A3GALT2	NM_001080438.1 link	c.598G>A	p.Val200Met	missense_variant	Exon 5 of 5	ENST00000442999.3	NP_001073907.1	U3KPV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
A3GALT2	ENST00000442999.3 link	c.598G>A	p.Val200Met	missense_variant	Exon 5 of 5	5	NM_001080438.1	ENSP00000475261.1		U3KPV4

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

GnomAD3 exomes

AF:

0.00468

AC:

683

AN:

145904

Hom.:

AF XY:

0.00482

AC XY:

390

AN XY:

80968

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 SAS exome

AF:

0.00141

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

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00321

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.0000298

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.00909

Gnomad4 OTH exome

AF:

0.00641

GnomAD4 genome

AF:

0.00542

AC:

824

AN:

152104

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

350

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.00896

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00777

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A3GALT2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.24

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0092

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over