chr8-30138707-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001100916.2(MBOAT4):c.169G>T(p.Gly57Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000452 in 1,550,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MBOAT4
NM_001100916.2 missense
NM_001100916.2 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 4.28
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]
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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 |
---|---|---|---|---|---|---|---|
MBOAT4 | NM_001100916.2 | c.169G>T | p.Gly57Cys | missense_variant | 2/3 | ENST00000320542.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBOAT4 | ENST00000320542.4 | c.169G>T | p.Gly57Cys | missense_variant | 2/3 | 1 | NM_001100916.2 | P1 | |
LEPROTL1 | ENST00000520739.5 | c.280-25404C>A | intron_variant, NMD_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000215 AC: 3AN: 1398104Hom.: 0 Cov.: 63 AF XY: 0.00000145 AC XY: 1AN XY: 689600
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74472
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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 submitter | clinical testing | Ambry Genetics | Jul 22, 2022 | The c.169G>T (p.G57C) 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 169, causing the glycine (G) at amino acid position 57 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of glycosylation at S58 (P = 0.0685);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at