NM_173800.5:c.1859G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_173800.5(LVRN):​c.1859G>T​(p.Gly620Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LVRN
NM_173800.5 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.49

Publications

1 publications found
Variant links:
Genes affected
LVRN (HGNC:26904): (laeverin) Predicted to enable metalloaminopeptidase activity; peptide binding activity; and zinc ion binding activity. Predicted to be involved in several processes, including peptide catabolic process; proteolysis; and regulation of blood pressure. Predicted to be integral component of membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LVRNNM_173800.5 linkc.1859G>T p.Gly620Val missense_variant Exon 11 of 20 ENST00000357872.9 NP_776161.3 Q6Q4G3-1Q0P5U8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LVRNENST00000357872.9 linkc.1859G>T p.Gly620Val missense_variant Exon 11 of 20 1 NM_173800.5 ENSP00000350541.4 Q6Q4G3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000400
AC:
1
AN:
250104
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458878
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725830
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33390
American (AMR)
AF:
0.00
AC:
0
AN:
44604
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26068
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39562
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85872
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5694
European-Non Finnish (NFE)
AF:
9.01e-7
AC:
1
AN:
1110008
Other (OTH)
AF:
0.00
AC:
0
AN:
60280
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000505
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.071
.;T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
.;M
PhyloP100
6.5
PrimateAI
Benign
0.45
T
PROVEAN
Pathogenic
-6.0
.;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0020
.;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.98
.;D
Vest4
0.76
MutPred
0.52
.;Gain of ubiquitination at K618 (P = 0.0505);
MVP
0.67
MPC
0.47
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.76
gMVP
0.64
Mutation Taster
=42/58
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1560079; hg19: chr5-115338570; API