Genetic Variant MGAT4C:p.Arg68Leu (chr12-85983615-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001351288.2(MGAT4C):c.203G>T(p.Arg68Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MGAT4C
NM_001351288.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Publications

4 publications found

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]

MGAT4C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40290758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351288.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGAT4C	NM_001351288.2	MANE Select	c.203G>T	p.Arg68Leu	missense	Exon 4 of 5	NP_001338217.1	Q9UBM8-1
MGAT4C	NM_001351282.2		c.317G>T	p.Arg106Leu	missense	Exon 5 of 6	NP_001338211.1
MGAT4C	NM_001351283.2		c.290G>T	p.Arg97Leu	missense	Exon 5 of 6	NP_001338212.1	Q9UBM8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGAT4C	ENST00000611864.5	TSL:5 MANE Select	c.203G>T	p.Arg68Leu	missense	Exon 4 of 5	ENSP00000481096.1	Q9UBM8-1
MGAT4C	ENST00000621808.5	TSL:1	c.203G>T	p.Arg68Leu	missense	Exon 8 of 9	ENSP00000478300.1	Q9UBM8-1
MGAT4C	ENST00000547225.5	TSL:1	c.203G>T	p.Arg68Leu	missense	Exon 5 of 6	ENSP00000449172.1	F8VWY2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000425

AC:

AN:

235484

AF XY:

0.00000783

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717760

African (AFR)

AF:

0.00

AC:

AN:

32442

American (AMR)

AF:

0.00

AC:

AN:

41868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25722

East Asian (EAS)

AF:

0.00

AC:

AN:

38266

South Asian (SAS)

AF:

0.00

AC:

AN:

83130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102942

Other (OTH)

AF:

0.00

AC:

AN:

59570

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.028

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

PhyloP100

5.9

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

REVEL

Benign

0.26

Sift

Benign

0.036

Sift4G

Benign

0.21

Polyphen

0.35

Vest4

0.69

MVP

0.20

ClinPred

0.84

GERP RS

4.6

Varity_R

0.20

gMVP

0.78

Mutation Taster

=28/72

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over