9-136984734-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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: 7.2e-7 (0 hom.)
• Consequence: LCNL1 NM_207510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11498737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCNL1	NM_207510.4	c.218G>C	p.Arg73Pro	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.218G>C	p.Arg73Pro	missense_variant	Exon 3 of 3	2	NM_207510.4	ENSP00000386162.2
ENSG00000284341	ENST00000471521.5	n.*214+171G>C		intron_variant	Intron 8 of 9	5		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

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: 9.37e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139879186;