chr9-136984783-G-A

Variant names:

• chr9-136984783-G-A
• rs201283961
• NM_207510.4:c.267G>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.267G>A​(p.Met89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M89T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LCNL1 NM_207510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 2 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=0.045407206).

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.267G>A	p.Met89Ile	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.267G>A	p.Met89Ile	missense	Exon 3 of 3	ENSP00000386162.2	Q6ZST4
	LCNL1	ENST00000460177.1	TSL:1	n.1240+220G>A		intron	N/A
	ENSG00000284341	ENST00000471521.5	TSL:5	n.*214+220G>A		intron	N/A	ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.26
DANN	Benign	0.72
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.0050
Sift	Benign	0.070	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.065
MutPred		0.41		Loss of MoRF binding (P = 0.1135)
MVP		0.014
MPC		0.23
ClinPred		0.035	T
GERP RS		-2.1
Varity_R		0.084
gMVP		0.33
Mutation Taster		=100/0	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: rs201283961; hg19: chr9-139879235;