Genetic Variant LCN6:p.Gly58Glu (chr9-136747481-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198946.3(LCN6):c.173G>A(p.Gly58Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 1,613,670 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 169 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 138 hom. )

Consequence

LCN6
NM_198946.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.430

Variant links:

Genes affected

LCN6 (HGNC:17337): (lipocalin 6) Predicted to enable small molecule binding activity. Predicted to be involved in single fertilization. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LCN6 links:

ENSG00000204003 (HGNC:):

ENSG00000204003 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027819574).

BP6

Variant 9-136747481-C-T is Benign according to our data. Variant chr9-136747481-C-T is described in ClinVar as [Benign]. Clinvar id is 776460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN6	NM_198946.3 link	c.173G>A	p.Gly58Glu	missense_variant	Exon 2 of 7	ENST00000341206.9	NP_945184.1	P62502A0A024R8I9
LOC100128593	NR_033913.1 link	n.445C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN6	ENST00000341206.9 link	c.173G>A	p.Gly58Glu	missense_variant	Exon 2 of 7	1	NM_198946.3	ENSP00000339621.3		P62502
ENSG00000204003	ENST00000435202.5 link	n.143G>A		non_coding_transcript_exon_variant	Exon 2 of 11	2		ENSP00000399627.1		H7C1C5

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3759

AN:

152136

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0862

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00667

AC:

1674

AN:

250840

Hom.:

AF XY:

0.00488

AC XY:

662

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.0906

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00251

AC:

3672

AN:

1461416

Hom.:

138

Cov.:

AF XY:

0.00216

AC XY:

1568

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0874

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.00586

GnomAD4 genome

AF:

0.0248

AC:

3780

AN:

152254

Hom.:

169

Cov.:

AF XY:

0.0238

AC XY:

1772

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0865

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0273

ESP6500AA

AF:

0.0831

AC:

366

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00809

AC:

982

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

REVEL

Benign

0.065

Sift

Benign

0.10

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.33

MVP

0.18

MPC

0.34

ClinPred

0.0093

GERP RS

2.0

Varity_R

0.12

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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