Genetic Variant LCN6:p.Val104Leu (chr9-136745272-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198946.3(LCN6):c.310G>T(p.Val104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,611,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V104M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LCN6
NM_198946.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11194301).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198946.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN6	NM_198946.3	MANE Select	c.310G>T	p.Val104Leu	missense	Exon 4 of 7	NP_945184.1	P62502

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCN6	ENST00000341206.9	TSL:1 MANE Select	c.310G>T	p.Val104Leu	missense	Exon 4 of 7	ENSP00000339621.3	P62502
LCN6	ENST00000476567.1	TSL:1	c.55G>T	p.Val19Leu	missense	Exon 2 of 3	ENSP00000468337.1	K7ERN5
ENSG00000204003	ENST00000435202.5	TSL:2	n.280G>T		non_coding_transcript_exon	Exon 4 of 11	ENSP00000399627.1	H7C1C5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250632

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459788

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0000946

AC:

AN:

52848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110616

Other (OTH)

AF:

0.0000166

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.59

M_CAP

Benign

0.0071

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

PhyloP100

0.13

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

REVEL

Benign

0.043

Sift

Benign

0.34

Sift4G

Uncertain

0.047

Polyphen

0.37

Vest4

0.20

MutPred

0.47

Gain of loop (P = 0.2754)

MVP

0.10

MPC

0.074

ClinPred

0.071

GERP RS

0.14

Varity_R

0.032

gMVP

0.46

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over