chr5-96979351-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005575.3(LNPEP):​c.233G>A​(p.Gly78Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LNPEP
NM_005575.3 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
Variant links:
Genes affected
LNPEP (HGNC:6656): (leucyl and cystinyl aminopeptidase) This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26966703).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LNPEPNM_005575.3 linkuse as main transcriptc.233G>A p.Gly78Asp missense_variant 2/18 ENST00000231368.10
LNPEPNM_175920.4 linkuse as main transcriptc.191G>A p.Gly64Asp missense_variant 2/18
LNPEPXM_047417177.1 linkuse as main transcriptc.233G>A p.Gly78Asp missense_variant 2/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LNPEPENST00000231368.10 linkuse as main transcriptc.233G>A p.Gly78Asp missense_variant 2/181 NM_005575.3 P1Q9UIQ6-1
LNPEPENST00000395770.3 linkuse as main transcriptc.191G>A p.Gly64Asp missense_variant 2/181 Q9UIQ6-2

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
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:
0.00144
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250614
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135396
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000868
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461776
Hom.:
0
Cov.:
33
AF XY:
0.0000234
AC XY:
17
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000403
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:
0.00000270
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152304
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00170
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:
0.00142
Bravo
AF:
0.000419
ExAC
AF:
0.0000247
AC:
3

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 GeneticsNov 18, 2023The c.233G>A (p.G78D) alteration is located in exon 2 (coding exon 2) of the LNPEP gene. This alteration results from a G to A substitution at nucleotide position 233, causing the glycine (G) at amino acid position 78 to be replaced by an aspartic acid (D). 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
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.093
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-2.3
N;N
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.80
MutPred
0.29
Loss of MoRF binding (P = 0.0521);.;
MVP
0.53
MPC
0.85
ClinPred
0.45
T
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.52

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: rs528454001; hg19: chr5-96315055; API