Genetic Variant NM_207510.4:c.335G>C (chr9-136984851-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207510.4(LCNL1):c.335G>C(p.Arg112Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,412,620 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LCNL1
NM_207510.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.53

Variant links:

Genes affected

LCNL1 (HGNC:34436): (lipocalin like 1) Predicted to enable small molecule binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LCNL1 links:

ENSG00000284341 (HGNC:):

ENSG00000284341 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056739897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCNL1	NM_207510.4 link	c.335G>C	p.Arg112Thr	missense_variant	Exon 3 of 3	ENST00000408973.3	NP_997393.3	Q6ZST4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCNL1	ENST00000408973.3 link	c.335G>C	p.Arg112Thr	missense_variant	Exon 3 of 3	2	NM_207510.4	ENSP00000386162.2		Q6ZST4
ENSG00000284341	ENST00000471521.5 link	n.*215-185G>C		intron_variant	Intron 8 of 9	5		ENSP00000435033.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1412620

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698086

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:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.5

DANN

Benign

0.64

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.28

M_CAP

Benign

0.0013

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.52

REVEL

Benign

0.019

Sift

Uncertain

0.016

Sift4G

Benign

0.14

Polyphen

0.31

Vest4

0.13

MutPred

0.34

Gain of phosphorylation at R112 (P = 0.0089);

MVP

0.030

MPC

0.39

ClinPred

0.090

GERP RS

-2.0

Varity_R

0.062

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over