chr9-136745203-C-G

Variant names:

• chr9-136745203-C-G
• rs753293850
• NM_198946.3:c.379G>C

Variant summary

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

The NM_198946.3(LCN6):​c.379G>C​(p.Gly127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,296 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LCN6 NM_198946.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 0 publications found

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

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=0.16829461).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198946.3. 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
	LCN6	NM_198946.3	MANE Select	c.379G>C	p.Gly127Arg	missense	Exon 4 of 7	NP_945184.1	P62502

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN6	ENST00000341206.9	TSL:1 MANE Select	c.379G>C	p.Gly127Arg	missense	Exon 4 of 7	ENSP00000339621.3	P62502
	LCN6	ENST00000476567.1	TSL:1	c.124G>C	p.Gly42Arg	missense	Exon 2 of 3	ENSP00000468337.1	K7ERN5
	ENSG00000204003	ENST00000435202.5	TSL:2	n.349G>C		non_coding_transcript_exon	Exon 4 of 11	ENSP00000399627.1	H7C1C5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461296 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726998

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111744

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.99
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.047
Sift	Benign	0.082	T
Sift4G	Benign	0.15	T
Polyphen		0.94	P
Vest4		0.16
MutPred		0.43		Gain of solvent accessibility (P = 0.0037)
MVP		0.29
MPC		0.24
ClinPred		0.91	D
GERP RS		1.5
Varity_R		0.060
gMVP		0.50
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs753293850; hg19: chr9-139639655;