Genetic Variant MGAT4D:p.Leu242Met (chr4-140461967-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001277353.2(MGAT4D):c.724T>A(p.Leu242Met) variant causes a missense change. The variant allele was found at a frequency of 0.259 in 699,112 control chromosomes in the GnomAD database, including 24,910 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4902 hom., cov: 30)

Exomes 𝑓: 0.26 ( 20008 hom. )

Consequence

MGAT4D
NM_001277353.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

Variant links:

Genes affected

MGAT4D (HGNC:43619): (MGAT4 family member D) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein N-linked glycosylation. Predicted to be located in membrane. Predicted to be active in Golgi stack; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

MGAT4D 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=0.0064281523).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT4D	NM_001277353.2 link	c.724T>A	p.Leu242Met	missense_variant	Exon 7 of 11	ENST00000511113.6	NP_001264282.1	A6NG13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT4D	ENST00000511113.6 link	c.724T>A	p.Leu242Met	missense_variant	Exon 7 of 11	5	NM_001277353.2	ENSP00000421185.1		A6NG13

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38061

AN:

151610

Hom.:

4905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.257

GnomAD3 exomes

AF:

0.287

AC:

38454

AN:

133848

Hom.:

5891

AF XY:

0.290

AC XY:

21140

AN XY:

72904

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.366

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.262

AC:

143296

AN:

547386

Hom.:

20008

Cov.:

AF XY:

0.267

AC XY:

79219

AN XY:

296350

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.251

AC:

38076

AN:

151726

Hom.:

4902

Cov.:

AF XY:

0.256

AC XY:

18977

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.319

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.252

Hom.:

985

Bravo

AF:

0.256

TwinsUK

AF:

0.231

AC:

857

ALSPAC

AF:

0.234

AC:

903

ExAC

AF:

0.276

AC:

4181

Asia WGS

AF:

0.340

AC:

1181

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.038

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0064

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

2.8

N;N

REVEL

Benign

0.065

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.14

ClinPred

0.0092

GERP RS

4.6

Varity_R

0.055

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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