22-50503411-T-G

Variant summary

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

The ENST00000474879.7(LMF2):ā€‹c.2104A>Cā€‹(p.Thr702Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,896 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

LMF2
ENST00000474879.7 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24
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]

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=0.051252723).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LMF2NM_033200.3 linkuse as main transcriptc.2104A>C p.Thr702Pro missense_variant 14/14 ENST00000474879.7 NP_149977.2 Q9BU23-1
LMF2NM_001363816.2 linkuse as main transcriptc.2029A>C p.Thr677Pro missense_variant 14/14 NP_001350745.1
LMF2XM_006724426.4 linkuse as main transcriptc.1939A>C p.Thr647Pro missense_variant 13/13 XP_006724489.1
LMF2XM_047441593.1 linkuse as main transcriptc.1102A>C p.Thr368Pro missense_variant 9/9 XP_047297549.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LMF2ENST00000474879.7 linkuse as main transcriptc.2104A>C p.Thr702Pro missense_variant 14/141 NM_033200.3 ENSP00000424381.1 Q9BU23-1
LMF2ENST00000216080.5 linkuse as main transcriptc.2029A>C p.Thr677Pro missense_variant 14/142 ENSP00000216080.5 Q9BU23-2
LMF2ENST00000504717.1 linkuse as main transcriptn.1083A>C non_coding_transcript_exon_variant 6/65

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152054
Hom.:
0
Cov.:
33
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:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000824
AC:
2
AN:
242772
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132764
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000549
AC:
8
AN:
1457842
Hom.:
0
Cov.:
29
AF XY:
0.00000827
AC XY:
6
AN XY:
725368
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152054
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74254
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000827
AC:
1

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 submitterclinical testingAmbry GeneticsJan 23, 2023The c.2104A>C (p.T702P) alteration is located in exon 14 (coding exon 14) of the LMF2 gene. This alteration results from a A to C substitution at nucleotide position 2104, causing the threonine (T) at amino acid position 702 to be replaced by a proline (P). 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
0.059
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.53
DANN
Benign
0.83
DEOGEN2
Benign
0.015
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.40
T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.95
N;N
REVEL
Benign
0.033
Sift
Benign
0.26
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.0
B;B
Vest4
0.068
MutPred
0.17
Gain of glycosylation at T702 (P = 0.0234);.;
MVP
0.014
ClinPred
0.031
T
GERP RS
-8.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.071
gMVP
0.077

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.

Other links and lift over

dbSNP: rs774758677; hg19: chr22-50941840; API