NM_207510.4:c.343C>A

Variant names:

• chr9-136984859-C-A
• rs1368603164
• NM_207510.4:c.343C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207510.4(LCNL1):​c.343C>A​(p.Arg115Ser) 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 1,409,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R115C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCNL1 NM_207510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 0 publications found

Genes affected

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

ENSG00000284341 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066968024).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207510.4. 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
	LCNL1	NM_207510.4	MANE Select	c.343C>A	p.Arg115Ser	missense	Exon 3 of 3	NP_997393.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCNL1	ENST00000408973.3	TSL:2 MANE Select	c.343C>A	p.Arg115Ser	missense	Exon 3 of 3	ENSP00000386162.2	Q6ZST4
	LCNL1	ENST00000460177.1	TSL:1	n.1241-177C>A		intron	N/A
	ENSG00000284341	ENST00000471521.5	TSL:5	n.*215-177C>A		intron	N/A	ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1409652 Hom.: 0 Cov.: 35 AF XY: 0.00000287 AC XY: 2 AN XY: 696418

African (AFR) AF: 0.00 AC: 0 AN: 32304

American (AMR) AF: 0.00 AC: 0 AN: 36528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25248

East Asian (EAS) AF: 0.00 AC: 0 AN: 36864

South Asian (SAS) AF: 0.00 AC: 0 AN: 80262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1084888

Other (OTH) AF: 0.00 AC: 0 AN: 58464

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.022
DANN	Benign	0.79
DEOGEN2	Benign	0.00035	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.8
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.012
Sift	Uncertain	0.011	D
Sift4G	Benign	0.14	T
Polyphen		0.44	B
Vest4		0.076
MutPred		0.27		Loss of MoRF binding (P = 0.0266)
MVP		0.014
MPC		0.22
ClinPred		0.13	T
GERP RS		-4.7
Varity_R		0.071
gMVP		0.20
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1368603164; hg19: chr9-139879311;