Variant 22-50503828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033200.3(LMF2):c.1795C>T(p.Leu599Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000406 in 1,453,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

LMF2
NM_033200.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

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:

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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	Protein
LMF2	NM_033200.3 linkuse as main transcript	c.1795C>T	p.Leu599Phe	missense_variant	13/14	ENST00000474879.7	NP_149977.2
LMF2	NM_001363816.2 linkuse as main transcript	c.1720C>T	p.Leu574Phe	missense_variant	13/14		NP_001350745.1
LMF2	XM_006724426.4 linkuse as main transcript	c.1630C>T	p.Leu544Phe	missense_variant	12/13		XP_006724489.1
LMF2	XM_047441593.1 linkuse as main transcript	c.793C>T	p.Leu265Phe	missense_variant	8/9		XP_047297549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF2	ENST00000474879.7 linkuse as main transcript	c.1795C>T	p.Leu599Phe	missense_variant	13/14	1	NM_033200.3	ENSP00000424381	P1	Q9BU23-1
LMF2	ENST00000216080.5 linkuse as main transcript	c.1720C>T	p.Leu574Phe	missense_variant	13/14	2		ENSP00000216080		Q9BU23-2
LMF2	ENST00000504717.1 linkuse as main transcript	n.774C>T		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

244594

Hom.:

AF XY:

0.0000226

AC XY:

AN XY:

132854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000266

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000406

AC:

AN:

1453794

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

723490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

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

Oct 17, 2023

The c.1795C>T (p.L599F) alteration is located in exon 13 (coding exon 13) of the LMF2 gene. This alteration results from a C to T substitution at nucleotide position 1795, causing the leucine (L) at amino acid position 599 to be replaced by a phenylalanine (F). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.026

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.98

D;D

Vest4

0.60

MutPred

0.58

Gain of helix (P = 0.0854);.;

MVP

0.040

ClinPred

0.61

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.66

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