7-101196059-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178176.4(MOGAT3):​c.913G>A​(p.Glu305Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,611,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

MOGAT3
NM_178176.4 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.634
Variant links:
Genes affected
MOGAT3 (HGNC:23249): (monoacylglycerol O-acyltransferase 3) Acyl-CoA:monoacylglycerol acyltransferase (MOGAT; EC 2.3.1.22) catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA (Cheng et al., 2003 [PubMed 12618427]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04147646).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MOGAT3NM_178176.4 linkc.913G>A p.Glu305Lys missense_variant Exon 7 of 7 ENST00000223114.9 NP_835470.1 Q86VF5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MOGAT3ENST00000223114.9 linkc.913G>A p.Glu305Lys missense_variant Exon 7 of 7 1 NM_178176.4 ENSP00000223114.4 Q86VF5-1
MOGAT3ENST00000379423.3 linkc.710G>A p.Arg237Gln missense_variant Exon 6 of 6 1 ENSP00000368734.3 Q86VF5-2
MOGAT3ENST00000440203.6 linkc.999G>A p.Pro333Pro synonymous_variant Exon 6 of 6 2 ENSP00000403756.2 Q86VF5-3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151908
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000417
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248398
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134670
show subpopulations
Gnomad AFR exome
AF:
0.000125
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:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1460016
Hom.:
1
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
726324
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.0000189
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151908
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74214
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000417
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.913G>A (p.E305K) alteration is located in exon 7 (coding exon 7) of the MOGAT3 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the glutamic acid (E) at amino acid position 305 to be replaced by a lysine (K). 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
0.10
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.16
DANN
Benign
0.90
DEOGEN2
Benign
0.0068
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.041
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.0080
Sift
Benign
0.26
T
Sift4G
Benign
0.47
T
Polyphen
0.23
B
Vest4
0.15
MVP
0.11
MPC
0.23
ClinPred
0.025
T
GERP RS
-3.5
Varity_R
0.096
gMVP
0.38

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: rs371428887; hg19: chr7-100839340; COSMIC: COSV56175096; API