12-85983615-C-T

Variant summary

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

The NM_001351288.2(MGAT4C):​c.203G>A​(p.Arg68His) variant causes a missense change. The variant allele was found at a frequency of 0.00000627 in 1,594,832 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

MGAT4C
NM_001351288.2 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
MGAT4C (HGNC:30871): (MGAT4 family member C) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein N-linked glycosylation. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24552843).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MGAT4CNM_001351288.2 linkuse as main transcriptc.203G>A p.Arg68His missense_variant 4/5 ENST00000611864.5 NP_001338217.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MGAT4CENST00000611864.5 linkuse as main transcriptc.203G>A p.Arg68His missense_variant 4/55 NM_001351288.2 ENSP00000481096 P1Q9UBM8-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000425
AC:
1
AN:
235484
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
127732
show subpopulations
Gnomad AFR exome
AF:
0.0000662
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000416
AC:
6
AN:
1442716
Hom.:
0
Cov.:
29
AF XY:
0.00000418
AC XY:
3
AN XY:
717760
show subpopulations
Gnomad4 AFR exome
AF:
0.0000308
Gnomad4 AMR exome
AF:
0.0000239
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJun 07, 2024The c.203G>A (p.R68H) alteration is located in exon 6 (coding exon 2) of the MGAT4C gene. This alteration results from a G to A substitution at nucleotide position 203, causing the arginine (R) at amino acid position 68 to be replaced by a histidine (H). 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
0.090
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T;T;T;T;.;.
Eigen
Benign
-0.00020
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.25
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M;M;M;M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.80
.;.;N;.;N;N;D
REVEL
Benign
0.12
Sift
Benign
0.058
.;.;T;.;T;T;D
Sift4G
Benign
0.14
T;T;T;T;T;.;D
Polyphen
0.0040
B;B;B;B;B;.;.
Vest4
0.28
MVP
0.29
ClinPred
0.85
D
GERP RS
4.6
Varity_R
0.098
gMVP
0.67

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.

Other links and lift over

dbSNP: rs200651947; hg19: chr12-86377393; API