chr2-98644038-G-A

Position:

chr2-98644038-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012214.3(MGAT4A):c.905C>T(p.Ala302Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 1,584,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

MGAT4A
NM_012214.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97

Variant links:

Genes affected

MGAT4A (HGNC:7047): (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A) This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme B, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [provided by RefSeq, Jul 2008]

MGAT4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22077766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT4A	NM_012214.3 linkuse as main transcript	c.905C>T	p.Ala302Val	missense_variant	10/16	ENST00000393487.6	NP_036346.1
MGAT4A	NM_001160154.2 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	7/13		NP_001153626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT4A	ENST00000393487.6 linkuse as main transcript	c.905C>T	p.Ala302Val	missense_variant	10/16	5	NM_012214.3	ENSP00000377127	P1	Q9UM21-1
MGAT4A	ENST00000264968.7 linkuse as main transcript	c.905C>T	p.Ala302Val	missense_variant	9/15	1		ENSP00000264968	P1	Q9UM21-1
MGAT4A	ENST00000409391.1 linkuse as main transcript	c.905C>T	p.Ala302Val	missense_variant	10/16	5		ENSP00000386841	P1	Q9UM21-1
MGAT4A	ENST00000414521.6 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	7/13	2		ENSP00000404889		Q9UM21-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000951

AC:

AN:

241910

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

130758

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000704

Gnomad FIN exome

AF:

0.000373

Gnomad NFE exome

AF:

0.0000542

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.0000768

AC:

110

AN:

1432166

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

710850

show subpopulations

Gnomad4 AFR exome

AF:

0.000306

Gnomad4 AMR exome

AF:

0.0000471

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000365

Gnomad4 FIN exome

AF:

0.000569

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.0000680

GnomAD4 genome

AF:

0.000112

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000812

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.905C>T (p.A302V) alteration is located in exon 10 (coding exon 9) of the MGAT4A gene. This alteration results from a C to T substitution at nucleotide position 905, causing the alanine (A) at amino acid position 302 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D;.

M_CAP

Benign

0.033

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.9

L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.018

D;D;D;D

Polyphen

0.97

D;D;.;D

Vest4

0.50

MVP

0.78

MPC

0.43

ClinPred

0.11

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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