9-136984734-G-C

Variant names:

• chr9-136984734-G-C
• rs200276332
• NM_207510.4:c.218G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207510.4(LCNL1):​c.218G>C​(p.Arg73Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R73Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LCNL1 NM_207510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• 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: 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=0.11498737).

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.218G>C	p.Arg73Pro	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.218G>C	p.Arg73Pro	missense	Exon 3 of 3	ENSP00000386162.2	Q6ZST4
	LCNL1	ENST00000460177.1	TSL:1	n.1240+171G>C		intron	N/A
	ENSG00000284341	ENST00000471521.5	TSL:5	n.*214+171G>C		intron	N/A	ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381732 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 677584

African (AFR) AF: 0.00 AC: 0 AN: 30916

American (AMR) AF: 0.00 AC: 0 AN: 37118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21464

East Asian (EAS) AF: 0.00 AC: 0 AN: 37142

South Asian (SAS) AF: 0.00 AC: 0 AN: 74612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5398

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067742

Other (OTH) AF: 0.00 AC: 0 AN: 56830

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.0060
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.047
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.021	D
Polyphen		0.0030	B
Vest4		0.24
MutPred		0.65		Loss of stability (P = 0.0777)
MVP		0.040
MPC		0.29
ClinPred		0.19	T
GERP RS		-0.11
Varity_R		0.65
gMVP		0.84
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs200276332; hg19: chr9-139879186;