10-88761469-C-G

Variant summary

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

The NM_001102469.2(LIPN):​c.64C>G​(p.Leu22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LIPN
NM_001102469.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.458
Variant links:
Genes affected
LIPN (HGNC:23452): (lipase family member N) The gene encodes a lipase that is highly expressed in granular keratinocytes in the epidermis, and plays a role in the differentiation of keratinocytes. Mutations in this gene are associated with lamellar ichthyosis type 4. [provided by RefSeq, Dec 2011]

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=0.054983944).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIPNNM_001102469.2 linkc.64C>G p.Leu22Val missense_variant Exon 2 of 10 ENST00000404459.2 NP_001095939.1 Q5VXI9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIPNENST00000404459.2 linkc.64C>G p.Leu22Val missense_variant Exon 2 of 10 1 NM_001102469.2 ENSP00000383923.1 Q5VXI9
LIPNENST00000674982.1 linkn.197C>G non_coding_transcript_exon_variant Exon 2 of 4

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151986
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460082
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726358
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151986
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74212
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.64C>G (p.L22V) alteration is located in exon 1 (coding exon 1) of the LIPN gene. This alteration results from a C to G substitution at nucleotide position 64, causing the leucine (L) at amino acid position 22 to be replaced by a valine (V). 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
0.076
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.022
DANN
Benign
0.36
DEOGEN2
Benign
0.0034
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.055
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.065
Sift
Benign
0.50
T
Sift4G
Benign
0.52
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.46
Gain of catalytic residue at L22 (P = 0.0293);
MVP
0.22
MPC
0.016
ClinPred
0.079
T
GERP RS
0.14
Varity_R
0.036
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1336568945; hg19: chr10-90521226; API