8-30138598-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001100916.2(MBOAT4):​c.278G>T​(p.Trp93Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MBOAT4
NM_001100916.2 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91
Variant links:
Genes affected
MBOAT4 (HGNC:32311): (membrane bound O-acyltransferase domain containing 4) Enables serine O-acyltransferase activity. Involved in peptidyl-serine octanoylation. Predicted to be located in endoplasmic reticulum. Predicted to be active in membrane. Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
LEPROTL1 (HGNC:6555): (leptin receptor overlapping transcript like 1) Enables identical protein binding activity. Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in endosome. [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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MBOAT4NM_001100916.2 linkuse as main transcriptc.278G>T p.Trp93Leu missense_variant 2/3 ENST00000320542.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MBOAT4ENST00000320542.4 linkuse as main transcriptc.278G>T p.Trp93Leu missense_variant 2/31 NM_001100916.2 P1Q96T53-1
LEPROTL1ENST00000520739.5 linkuse as main transcriptc.280-25513C>A intron_variant, NMD_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000654
AC:
1
AN:
152944
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81158
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000405
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:
0.00000143
AC:
2
AN:
1399374
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
690200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
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:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

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 GeneticsJul 25, 2023The c.278G>T (p.W93L) alteration is located in exon 2 (coding exon 2) of the MBOAT4 gene. This alteration results from a G to T substitution at nucleotide position 278, causing the tryptophan (W) at amino acid position 93 to be replaced by a leucine (L). 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
0.52
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.68
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0080
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.96
P
Vest4
0.60
MutPred
0.66
Loss of catalytic residue at W93 (P = 0.0031);
MVP
0.50
ClinPred
0.95
D
GERP RS
5.4
Varity_R
0.58
gMVP
0.75

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: rs1207917140; hg19: chr8-29996114; API