Variant 8-30137289-C-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.344+1243G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,551,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

MBOAT4
NM_001100916.2 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.230

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:

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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=0.05207038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBOAT4	NM_001100916.2 linkuse as main transcript	c.344+1243G>T		intron_variant		ENST00000320542.4
LEPROTL1	NM_001128208.2 linkuse as main transcript	c.297C>A	p.Phe99Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT4	ENST00000320542.4 linkuse as main transcript	c.344+1243G>T		intron_variant		1	NM_001100916.2	P1	Q96T53-1
LEPROTL1	ENST00000523116.5 linkuse as main transcript	c.297C>A	p.Phe99Leu	missense_variant	4/4	2			O95214-2
LEPROTL1	ENST00000442880.6 linkuse as main transcript	c.412C>A	p.Leu138Ile	missense_variant	5/5	2
LEPROTL1	ENST00000520739.5 linkuse as main transcript	c.280-26822C>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000478

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

153952

Hom.:

AF XY:

0.0000490

AC XY:

AN XY:

81684

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000353

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:

0.000231

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1399328

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

690178

show subpopulations

Gnomad4 AFR exome

AF:

0.000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000278

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000144

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:

0.000473

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000447

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Oct 18, 2021

The c.297C>A (p.F99L) alteration is located in exon 4 (coding exon 4) of the LEPROTL1 gene. This alteration results from a C to A substitution at nucleotide position 297, causing the phenylalanine (F) at amino acid position 99 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

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.3

DANN

Benign

0.95

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.37

M_CAP

Benign

0.011

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

REVEL

Benign

0.067

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.060

Vest4

0.11

MutPred

0.42

Gain of ubiquitination at K102 (P = 0.1067);

MVP

0.043

MPC

0.70

ClinPred

0.042

GERP RS

0.045

gMVP

0.37

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