chr9-136757143-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178469.4(LCN8):​c.50G>A​(p.Gly17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LCN8
NM_178469.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.580
Variant links:
Genes affected
LCN8 (HGNC:27038): (lipocalin 8) Members of the lipocalin family, such as LCN8, have a common structure consisting of an 8-stranded antiparallel beta-barrel that forms a cup-shaped ligand-binding pocket or calyx. Lipocalins generally bind small hydrophobic ligands and transport them to specific cells (Suzuki et al., 2004 [PubMed 15363845]).[supplied by OMIM, Aug 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LCN8NM_178469.4 linkc.50G>A p.Gly17Asp missense_variant Exon 2 of 7 ENST00000371688.8 NP_848564.2 Q6JVE9-2A0A384MDK0Q6ZT51
LCN8NM_001345934.2 linkc.119G>A p.Gly40Asp missense_variant Exon 2 of 7 NP_001332863.1 Q6JVE9-1Q8NBE9
LCN8XM_017014272.3 linkc.119G>A p.Gly40Asp missense_variant Exon 2 of 6 XP_016869761.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LCN8ENST00000371688.8 linkc.50G>A p.Gly17Asp missense_variant Exon 2 of 7 1 NM_178469.4 ENSP00000360753.3 Q6JVE9-2

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
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
GnomAD3 exomes
AF:
0.0000202
AC:
5
AN:
247932
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134370
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000873
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000894
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1460764
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
726598
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000896
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:
0.0000153
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152358
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000523
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:
0.000110
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.50G>A (p.G17D) alteration is located in exon 2 (coding exon 2) of the LCN8 gene. This alteration results from a G to A substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 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
0.90
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.075
.;T
Eigen
Benign
-0.068
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.0091
T
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.4
D;.
REVEL
Benign
0.20
Sift
Uncertain
0.0050
D;.
Sift4G
Uncertain
0.0070
D;D
Polyphen
0.99
D;D
Vest4
0.80
MVP
0.33
MPC
0.72
ClinPred
0.90
D
GERP RS
2.5
Varity_R
0.37
gMVP
0.93

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: rs200546113; hg19: chr9-139651595; API