Variant 22-50503677-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000474879.7(LMF2):c.1838G>A(p.Arg613His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000741 in 918,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R613C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

LMF2
ENST00000474879.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.286

Variant links:

Genes affected

LMF2 (HGNC:25096): (lipase maturation factor 2) Predicted to be involved in protein maturation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LMF2 links:

LMF2 (HGNC:):

LMF2 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=0.05640775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF2	NM_033200.3 linkuse as main transcript	c.1838G>A	p.Arg613His	missense_variant	14/14	ENST00000474879.7	NP_149977.2	Q9BU23-1
LMF2	NM_001363816.2 linkuse as main transcript	c.1763G>A	p.Arg588His	missense_variant	14/14		NP_001350745.1
LMF2	XM_006724426.4 linkuse as main transcript	c.1673G>A	p.Arg558His	missense_variant	13/13		XP_006724489.1
LMF2	XM_047441593.1 linkuse as main transcript	c.836G>A	p.Arg279His	missense_variant	9/9		XP_047297549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LMF2	ENST00000474879.7 linkuse as main transcript	c.1838G>A	p.Arg613His	missense_variant	14/14	1	NM_033200.3	ENSP00000424381.1	Q9BU23-1
LMF2	ENST00000216080.5 linkuse as main transcript	c.1763G>A	p.Arg588His	missense_variant	14/14	2		ENSP00000216080.5	Q9BU23-2
LMF2	ENST00000504717.1 linkuse as main transcript	n.817G>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000764

AC:

AN:

130844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00340

Gnomad NFE

AF:

0.000146

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000582

AC:

AN:

223374

Hom.:

AF XY:

0.0000492

AC XY:

AN XY:

122002

show subpopulations

Gnomad AFR exome

AF:

0.0000669

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000115

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000972

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.0000737

AC:

AN:

787168

Hom.:

Cov.:

AF XY:

0.0000846

AC XY:

AN XY:

401946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000539

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000273

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000884

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000764

AC:

AN:

130950

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

62710

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000146

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000248

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

May 26, 2022

The c.1838G>A (p.R613H) alteration is located in exon 14 (coding exon 14) of the LMF2 gene. This alteration results from a G to A substitution at nucleotide position 1838, causing the arginine (R) at amino acid position 613 to be replaced by a histidine (H). 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

0.077

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.054

Sift

Benign

0.054

T;T

Sift4G

Uncertain

0.047

D;T

Polyphen

0.048

B;B

Vest4

0.10

MVP

0.014

ClinPred

0.041

GERP RS

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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