NM_022773.4:c.514G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_022773.4(LMF1):c.514G>A(p.Gly172Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000463 in 1,599,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

LMF1
NM_022773.4 missense, splice_region

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.63

Publications

5 publications found

Variant links:

Genes affected

LMF1 (HGNC:14154): (lipase maturation factor 1) Involved in triglyceride metabolic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. Implicated in familial lipase maturation factor 1 deficiency. [provided by Alliance of Genome Resources, Apr 2022]

LMF1 links:

LMF1-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

LMF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 16-934244-C-T is Pathogenic according to our data. Variant chr16-934244-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1399714.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMF1	NM_022773.4	MANE Select	c.514G>A	p.Gly172Arg	missense splice_region	Exon 3 of 11	NP_073610.2	Q96S06-1
LMF1	NM_001352020.1		c.514G>A	p.Gly172Arg	missense splice_region	Exon 3 of 11	NP_001338949.1
LMF1	NM_001352019.2		c.187G>A	p.Gly63Arg	missense splice_region	Exon 3 of 11	NP_001338948.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514G>A	p.Gly172Arg	missense splice_region	Exon 3 of 11	ENSP00000262301.12	Q96S06-1
LMF1	ENST00000562380.5	TSL:4	c.397G>A	p.Gly133Ser	missense	Exon 3 of 4	ENSP00000455715.1	H3BQC9
LMF1	ENST00000963976.1		c.514G>A	p.Gly172Arg	missense splice_region	Exon 3 of 12	ENSP00000634035.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000768

AC:

AN:

234488

AF XY:

0.0000468

show subpopulations

Gnomad AFR exome

AF:

0.0000661

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000565

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000825

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.0000449

AC:

AN:

1446992

Hom.:

Cov.:

AF XY:

0.0000375

AC XY:

AN XY:

720162

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.000134

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000202

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38970

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1111734

Other (OTH)

AF:

0.000166

AC:

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.000196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000428

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000839

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.0040

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.79

MutationAssessor

Pathogenic

3.4

PhyloP100

3.6

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Vest4

0.81

MutPred

0.60

Gain of catalytic residue at G172 (P = 0.0516)

MVP

0.36

MPC

0.054

ClinPred

0.65

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.87

gMVP

0.78

Mutation Taster

=16/84

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.58

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over