9-136984782-T-C

Variant names:

• chr9-136984782-T-C
• rs749220779
• NM_207510.4:c.266T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207510.4(LCNL1):​c.266T>C​(p.Met89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,421,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000021 (0 hom.)
• Consequence: LCNL1 NM_207510.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500

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

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=0.03693214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCNL1	NM_207510.4	c.266T>C	p.Met89Thr	missense_variant	Exon 3 of 3	ENST00000408973.3	NP_997393.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCNL1	ENST00000408973.3	c.266T>C	p.Met89Thr	missense_variant	Exon 3 of 3	2	NM_207510.4	ENSP00000386162.2
ENSG00000284341	ENST00000471521.5	n.*214+219T>C		intron_variant	Intron 8 of 9	5		ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000211 AC: 30 AN: 1421510 Hom.: 0 Cov.: 35 AF XY: 0.0000270 AC XY: 19 AN XY: 702444

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: 0.0000248

Gnomad4 OTH exome AF: 0.0000513

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 07, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.54
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.2	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.068
Sift	Benign	0.22	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.48		Loss of stability (P = 0.0265);
MVP		0.014
MPC		0.22
ClinPred		0.054	T
GERP RS		3.0
Varity_R		0.040
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs749220779; hg19: chr9-139879234;