Genetic Variant LMF1:p.Phe171Tyr (chr16-934246-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022773.4(LMF1):c.512T>A(p.Phe171Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000691 in 1,447,008 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F171S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LMF1
NM_022773.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.25

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.512T>A	p.Phe171Tyr	missense splice_region	Exon 3 of 11	NP_073610.2	Q96S06-1
LMF1	NM_001352020.1		c.512T>A	p.Phe171Tyr	missense splice_region	Exon 3 of 11	NP_001338949.1
LMF1	NM_001352019.2		c.185T>A	p.Phe62Tyr	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.512T>A	p.Phe171Tyr	missense splice_region	Exon 3 of 11	ENSP00000262301.12	Q96S06-1
LMF1	ENST00000562380.5	TSL:4	c.395T>A	p.Phe132Tyr	missense	Exon 3 of 4	ENSP00000455715.1	H3BQC9
LMF1	ENST00000963976.1		c.512T>A	p.Phe171Tyr	missense splice_region	Exon 3 of 12	ENSP00000634035.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447008

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111716

Other (OTH)

AF:

0.00

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.4

PhyloP100

4.3

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.1

REVEL

Benign

0.24

Sift

Benign

0.27

Sift4G

Benign

0.27

Vest4

0.63

MutPred

0.85

Gain of sheet (P = 0.1208)

MVP

0.28

MPC

0.059

ClinPred

0.47

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.52

Mutation Taster

=71/29

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over