Variant 8-30132640-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001100916.2(MBOAT4):c.611C>T(p.Ala204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,551,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

MBOAT4
NM_001100916.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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]

MBOAT4 links:

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]

LEPROTL1 links:

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=0.042007565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBOAT4	NM_001100916.2 linkuse as main transcript	c.611C>T	p.Ala204Val	missense_variant	3/3	ENST00000320542.4
LEPROTL1	NM_001128208.2 linkuse as main transcript	c.280-4632G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT4	ENST00000320542.4 linkuse as main transcript	c.611C>T	p.Ala204Val	missense_variant	3/3	1	NM_001100916.2	P1	Q96T53-1
LEPROTL1	ENST00000442880.6 linkuse as main transcript	c.394+151G>A		intron_variant		2
LEPROTL1	ENST00000523116.5 linkuse as main transcript	c.280-4632G>A		intron_variant		2			O95214-2
LEPROTL1	ENST00000520739.5 linkuse as main transcript	c.279+28154G>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000131

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:

0.000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000281

AC:

AN:

156308

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

82822

show subpopulations

Gnomad AFR exome

AF:

0.000126

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:

0.000119

Gnomad NFE exome

AF:

0.000680

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000714

AC:

999

AN:

1399446

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

474

AN XY:

690240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000889

Gnomad4 OTH exome

AF:

0.000552

GnomAD4 genome

AF:

0.000407

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000670

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.000192

AC:

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

Aug 10, 2021

The c.611C>T (p.A204V) alteration is located in exon 3 (coding exon 3) of the MBOAT4 gene. This alteration results from a C to T substitution at nucleotide position 611, causing the alanine (A) at amino acid position 204 to be replaced by a valine (V). 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

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.080

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.57

M_CAP

Benign

0.016

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.66

REVEL

Benign

0.096

Sift

Benign

0.30

Sift4G

Benign

0.36

Polyphen

0.0050

Vest4

0.092

MVP

0.70

ClinPred

0.012

GERP RS

2.0

Varity_R

0.053

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over