9-136755481-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000371688.8(LCN8):ā€‹c.262G>Cā€‹(p.Glu88Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

LCN8
ENST00000371688.8 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.370
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07685736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LCN8NM_178469.4 linkuse as main transcriptc.262G>C p.Glu88Gln missense_variant 4/7 ENST00000371688.8 NP_848564.2
LCN8NM_001345934.2 linkuse as main transcriptc.331G>C p.Glu111Gln missense_variant 4/7 NP_001332863.1
LCN8XM_017014272.3 linkuse as main transcriptc.331G>C p.Glu111Gln missense_variant 4/6 XP_016869761.1
LCN8XR_007061246.1 linkuse as main transcriptn.972G>C non_coding_transcript_exon_variant 1/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LCN8ENST00000371688.8 linkuse as main transcriptc.262G>C p.Glu88Gln missense_variant 4/71 NM_178469.4 ENSP00000360753 P2Q6JVE9-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460726
Hom.:
0
Cov.:
64
AF XY:
0.00000413
AC XY:
3
AN XY:
726672
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000756

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 GeneticsDec 26, 2023The c.262G>C (p.E88Q) alteration is located in exon 4 (coding exon 4) of the LCN8 gene. This alteration results from a G to C substitution at nucleotide position 262, causing the glutamic acid (E) at amino acid position 88 to be replaced by a glutamine (Q). 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
0.10
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
5.6
DANN
Benign
0.83
DEOGEN2
Benign
0.0026
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0057
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.077
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.5
.;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.0090
Sift
Benign
0.60
T;.
Sift4G
Uncertain
0.017
D;D
Polyphen
0.090
B;.
Vest4
0.29
MVP
0.33
MPC
0.27
ClinPred
0.051
T
GERP RS
0.64
Varity_R
0.039
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs567949310; hg19: chr9-139649933; API