Variant 22-50503488-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_033200.3(LMF2):c.2027C>T(p.Pro676Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,590,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

LMF2
NM_033200.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0510

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:

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=0.01953873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LMF2	NM_033200.3 linkuse as main transcript	c.2027C>T	p.Pro676Leu	missense_variant	14/14	ENST00000474879.7	NP_149977.2
LMF2	NM_001363816.2 linkuse as main transcript	c.1952C>T	p.Pro651Leu	missense_variant	14/14		NP_001350745.1
LMF2	XM_006724426.4 linkuse as main transcript	c.1862C>T	p.Pro621Leu	missense_variant	13/13		XP_006724489.1
LMF2	XM_047441593.1 linkuse as main transcript	c.1025C>T	p.Pro342Leu	missense_variant	9/9		XP_047297549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF2	ENST00000474879.7 linkuse as main transcript	c.2027C>T	p.Pro676Leu	missense_variant	14/14	1	NM_033200.3	ENSP00000424381	P1	Q9BU23-1
LMF2	ENST00000216080.5 linkuse as main transcript	c.1952C>T	p.Pro651Leu	missense_variant	14/14	2		ENSP00000216080		Q9BU23-2
LMF2	ENST00000504717.1 linkuse as main transcript	n.1006C>T		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000120

AC:

AN:

225430

Hom.:

AF XY:

0.000145

AC XY:

AN XY:

124056

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000394

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:

0.000145

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.000124

AC:

179

AN:

1438212

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

715030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000423

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000125

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000124

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 16, 2022

The c.2027C>T (p.P676L) alteration is located in exon 14 (coding exon 14) of the LMF2 gene. This alteration results from a C to T substitution at nucleotide position 2027, causing the proline (P) at amino acid position 676 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

Benign

0.075

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.9

DANN

Benign

0.74

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.013

Sift

Benign

0.18

T;T

Sift4G

Uncertain

0.018

D;D

Polyphen

0.0010

B;B

Vest4

0.056

MVP

0.030

ClinPred

0.017

GERP RS

-0.95

Varity_R

0.020

gMVP

0.25

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