2-98636588-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_012214.3(MGAT4A):āc.1330T>Cā(p.Phe444Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
MGAT4A
NM_012214.3 missense
NM_012214.3 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 8.44
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.801
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MGAT4A | ENST00000393487.6 | c.1330T>C | p.Phe444Leu | missense_variant | 13/16 | 5 | NM_012214.3 | ENSP00000377127.1 | ||
MGAT4A | ENST00000264968.7 | c.1330T>C | p.Phe444Leu | missense_variant | 12/15 | 1 | ENSP00000264968.2 | |||
MGAT4A | ENST00000409391.1 | c.1330T>C | p.Phe444Leu | missense_variant | 13/16 | 5 | ENSP00000386841.1 | |||
MGAT4A | ENST00000414521.6 | c.946T>C | p.Phe316Leu | missense_variant | 10/13 | 2 | ENSP00000404889.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251374Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135878
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460530Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 726704
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
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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 | Apr 22, 2022 | The c.1330T>C (p.F444L) alteration is located in exon 13 (coding exon 12) of the MGAT4A gene. This alteration results from a T to C substitution at nucleotide position 1330, causing the phenylalanine (F) at amino acid position 444 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
D;D;.;D
Vest4
MutPred
Gain of disorder (P = 0.1014);Gain of disorder (P = 0.1014);.;Gain of disorder (P = 0.1014);
MVP
MPC
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at