rs201224621

Variant names:

• chr9-136745263-G-C
• rs201224621
• NM_198946.3:c.319C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-136745263-G-C
• chr9-136745263-G-T

Variant summary

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

The NM_198946.3(LCN6):​c.319C>G​(p.Leu107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCN6 NM_198946.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

Genes affected

LCN6 (HGNC:17337): (lipocalin 6) Predicted to enable small molecule binding activity. Predicted to be involved in single fertilization. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000204003 (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=0.04573956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN6	NM_198946.3	c.319C>G	p.Leu107Val	missense_variant	Exon 4 of 7	ENST00000341206.9	NP_945184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN6	ENST00000341206.9	c.319C>G	p.Leu107Val	missense_variant	Exon 4 of 7	1	NM_198946.3	ENSP00000339621.3
ENSG00000204003	ENST00000435202.5	n.289C>G		non_coding_transcript_exon_variant	Exon 4 of 11	2		ENSP00000399627.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250742 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135794

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460654 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726680

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.64
DEOGEN2	Benign	0.0032	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.84	N;.
REVEL	Benign	0.062
Sift	Benign	1.0	T;.
Sift4G	Uncertain	0.028	D;D
Polyphen		0.22	B;.
Vest4		0.24
MutPred		0.36		Gain of sheet (P = 0.1208);.;
MVP		0.055
MPC		0.070
ClinPred		0.060	T
GERP RS		0.50
Varity_R		0.034
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201224621; hg19: chr9-139639715;