Variant 9-136757158-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_178469.4(LCN8):c.35T>C(p.Phe12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,240 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 1 hom. )

Consequence

LCN8
NM_178469.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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:

LCN8 (HGNC:):

LCN8 links:

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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	UniProt
LCN8	NM_178469.4 linkuse as main transcript	c.35T>C	p.Phe12Ser	missense_variant	2/7	ENST00000371688.8	NP_848564.2	Q6JVE9-2A0A384MDK0Q6ZT51
LCN8	NM_001345934.2 linkuse as main transcript	c.104T>C	p.Phe35Ser	missense_variant	2/7		NP_001332863.1	Q6JVE9-1Q8NBE9
LCN8	XM_017014272.3 linkuse as main transcript	c.104T>C	p.Phe35Ser	missense_variant	2/6		XP_016869761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LCN8	ENST00000371688.8 linkuse as main transcript	c.35T>C	p.Phe12Ser	missense_variant	2/7	1	NM_178469.4	ENSP00000360753.3	Q6JVE9-2
LCN8	ENST00000612714.1 linkuse as main transcript	c.104T>C	p.Phe35Ser	missense_variant	2/7	1		ENSP00000482512.1	Q6JVE9-1
LCN8	ENST00000479767.1 linkuse as main transcript	n.300T>C		non_coding_transcript_exon_variant	1/6	1
LCN8	ENST00000482893.1 linkuse as main transcript	n.381T>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246780

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0000666

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460240

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726262

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

May 20, 2024

The c.35T>C (p.F12S) alteration is located in exon 2 (coding exon 2) of the LCN8 gene. This alteration results from a T to C substitution at nucleotide position 35, causing the phenylalanine (F) at amino acid position 12 to be replaced by a serine (S). 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

0.91

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0079

.;T

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.2

D;.

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.59

MutPred

0.49

.;Gain of disorder (P = 0.0836);

MVP

0.31

MPC

0.86

ClinPred

0.83

GERP RS

3.5

Varity_R

0.28

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

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