Variant 9-136755462-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000371688.8(LCN8):c.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,613,294 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 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

LCN8
ENST00000371688.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.658

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]

LCN8 links:

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/exons	MANE	Protein
LCN8	NM_178469.4 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/7	ENST00000371688.8	NP_848564.2
LCN8	NM_001345934.2 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	4/7		NP_001332863.1
LCN8	XM_017014272.3 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	4/6		XP_016869761.1
LCN8	XR_007061246.1 linkuse as main transcript	n.991G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN8	ENST00000371688.8 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/7	1	NM_178469.4	ENSP00000360753	P2	Q6JVE9-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000104

AC:

AN:

250016

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1460918

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000105

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.281G>A (p.R94Q) alteration is located in exon 4 (coding exon 4) of the LCN8 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 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

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.12

Sift

Benign

0.31

T;.

Sift4G

Uncertain

0.020

D;D

Polyphen

0.96

D;.

Vest4

0.27

MVP

0.40

MPC

0.52

ClinPred

0.12

GERP RS

2.4

Varity_R

0.095

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: -2

DS_DG_spliceai

0.27

Position offset: -1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over