11-75727445-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_025098.4(MOGAT2):​c.281C>A​(p.Thr94Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,870 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 (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MOGAT2
NM_025098.4 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53
Variant links:
Genes affected
MOGAT2 (HGNC:23248): (monoacylglycerol O-acyltransferase 2) The protein encoded by this gene is an enzyme that catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. The encoded protein is important in the uptake of dietary fat by the small intestine. This protein forms a complex with diacylglycerol O-acyltransferase 2 in the endoplasmic reticulum, and this complex catalyzes the synthesis of triacylglycerol. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MOGAT2NM_025098.4 linkc.281C>A p.Thr94Asn missense_variant Exon 3 of 6 ENST00000198801.10 NP_079374.2 Q3SYC2-1
MOGAT2XM_011545267.2 linkc.281C>A p.Thr94Asn missense_variant Exon 3 of 6 XP_011543569.1
MOGAT2XM_024448696.2 linkc.35C>A p.Thr12Asn missense_variant Exon 3 of 6 XP_024304464.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MOGAT2ENST00000198801.10 linkc.281C>A p.Thr94Asn missense_variant Exon 3 of 6 1 NM_025098.4 ENSP00000198801.5 Q3SYC2-1
MOGAT2ENST00000526712.1 linkc.35C>A p.Thr12Asn missense_variant Exon 2 of 5 2 ENSP00000436283.1 Q3SYC2-2
MOGAT2ENST00000525093.5 linkn.281C>A non_coding_transcript_exon_variant Exon 3 of 5 2 ENSP00000436537.1 Q3SYC2-3

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251072
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.000308
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:
0.0000123
AC:
18
AN:
1461692
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.00
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:
0.0000167
Hom.:
0
Bravo
AF:
0.000125
ESP6500AA
AF:
0.000682
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.281C>A (p.T94N) alteration is located in exon 3 (coding exon 3) of the MOGAT2 gene. This alteration results from a C to A substitution at nucleotide position 281, causing the threonine (T) at amino acid position 94 to be replaced by an asparagine (N). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.
Eigen
Pathogenic
0.95
Eigen_PC
Pathogenic
0.92
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.073
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Benign
-0.83
T
MutationAssessor
Pathogenic
3.6
H;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-4.7
D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.029
D;D
Polyphen
1.0
D;.
Vest4
0.93
MVP
0.70
MPC
0.50
ClinPred
0.98
D
GERP RS
6.0
Varity_R
0.93
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs146955056; hg19: chr11-75438490; API