9-136764430-G-A

Position:

• chr9-136764430-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203347.2(LCN15):​c.59C>T​(p.Ala20Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCN15 NM_203347.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.560

Genes affected

LCN15 (HGNC:33777): (lipocalin 15) Predicted to enable small molecule binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LCN15 (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=0.08270806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN15	NM_203347.2	c.59C>T	p.Ala20Val	missense_variant	1/7	ENST00000316144.6	NP_976222.1
LCN15	XM_011518672.2	c.-27C>T		5_prime_UTR_premature_start_codon_gain_variant	1/7		XP_011516974.1
LCN15	XM_011518672.2	c.-27C>T		5_prime_UTR_variant	1/7		XP_011516974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN15	ENST00000316144.6	c.59C>T	p.Ala20Val	missense_variant	1/7	1	NM_203347.2	ENSP00000313833.5
LCN15	ENST00000482511.1	n.1826C>T		non_coding_transcript_exon_variant	1/6	1
LCN15	ENST00000495223.1	n.35C>T		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2022

The c.59C>T (p.A20V) alteration is located in exon 1 (coding exon 1) of the LCN15 gene. This alteration results from a C to T substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.024
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.52		Loss of helix (P = 0.1299);
MVP		0.055
MPC		0.17
ClinPred		0.55	D
GERP RS		2.0
Varity_R		0.18
gMVP		0.54

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: rs1389633946; hg19: chr9-139658882;