Variant 3-138124634-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016161.3(A4GNT):c.653C>A(p.Ala218Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,613,930 control chromosomes in the GnomAD database, including 365,185 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.66 ( 33420 hom., cov: 33)

Exomes 𝑓: 0.67 ( 331765 hom. )

Consequence

A4GNT
NM_016161.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.352

Variant links:

Genes affected

A4GNT (HGNC:17968): (alpha-1,4-N-acetylglucosaminyltransferase) This gene encodes a protein from the glycosyltransferase 32 family. The enzyme catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. It forms a unique glycan, GlcNAcalpha1-->4Galbeta-->R and is largely associated with the Golgi apparatus membrane. [provided by RefSeq, Jul 2008]

A4GNT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3401583E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A4GNT	NM_016161.3 linkuse as main transcript	c.653C>A	p.Ala218Asp	missense_variant	3/3	ENST00000236709.4	NP_057245.1	Q9UNA3
A4GNT	XM_017006543.3 linkuse as main transcript	c.653C>A	p.Ala218Asp	missense_variant	3/3		XP_016862032.1	Q9UNA3
A4GNT	XM_017006544.2 linkuse as main transcript	c.653C>A	p.Ala218Asp	missense_variant	3/3		XP_016862033.1	Q9UNA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A4GNT	ENST00000236709.4 linkuse as main transcript	c.653C>A	p.Ala218Asp	missense_variant	3/3	1	NM_016161.3	ENSP00000236709.3		Q9UNA3

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100730

AN:

151952

Hom.:

33389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.672

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.654

AC:

164344

AN:

251294

Hom.:

53999

AF XY:

0.656

AC XY:

89103

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.630

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.670

Gnomad SAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.662

GnomAD4 exome

AF:

0.673

AC:

983924

AN:

1461860

Hom.:

331765

Cov.:

AF XY:

0.672

AC XY:

488644

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.649

Gnomad4 AMR exome

AF:

0.642

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.630

Gnomad4 FIN exome

AF:

0.639

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.663

AC:

100810

AN:

152070

Hom.:

33420

Cov.:

AF XY:

0.663

AC XY:

49254

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.653

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.678

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.632

Gnomad4 FIN

AF:

0.634

Gnomad4 NFE

AF:

0.669

Gnomad4 OTH

AF:

0.671

Alfa

AF:

0.668

Hom.:

27651

Bravo

AF:

0.667

TwinsUK

AF:

0.689

AC:

2553

ALSPAC

AF:

0.678

AC:

2614

ESP6500AA

AF:

0.643

AC:

2835

ESP6500EA

AF:

0.669

AC:

5756

ExAC

AF:

0.652

AC:

79171

Asia WGS

AF:

0.607

AC:

2114

AN:

3478

EpiCase

AF:

0.668

EpiControl

AF:

0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.12

DANN

Benign

0.26

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.015

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.28

PrimateAI

Benign

0.27

PROVEAN

Benign

0.21

REVEL

Benign

0.16

Sift

Benign

0.91

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.024

MPC

0.16

ClinPred

0.0067

GERP RS

-1.8

Varity_R

0.091

gMVP

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over