5-135951340-T-G

Variant names:

• chr5-135951340-T-G
• rs31517
• NM_002302.3:c.172A>C

Variant summary

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

The NM_002302.3(LECT2):​c.172A>C​(p.Ile58Leu) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I58V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LECT2 NM_002302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

Genes affected

LECT2 (HGNC:6550): (leukocyte cell derived chemotaxin 2) This gene encodes a secreted, 16 kDa protein that acts as a chemotactic factor to neutrophils and stimulates the growth of chondrocytes and osteoblasts. This protein has high sequence similarity to the chondromodulin repeat regions of the chicken myb-induced myeloid 1 protein. A polymorphism in this gene may be associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

FBXL21P (HGNC:13600): (F-box and leucine rich repeat protein 21, pseudogene) This locus represents a transcribed pseudogene that is related to genes encoding members of the F-box family of proteins. [provided by RefSeq, Nov 2017]

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=0.10426819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LECT2	NM_002302.3	c.172A>C	p.Ile58Leu	missense_variant	Exon 3 of 4	ENST00000274507.6	NP_002293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LECT2	ENST00000274507.6	c.172A>C	p.Ile58Leu	missense_variant	Exon 3 of 4	1	NM_002302.3	ENSP00000274507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.6
DANN	Benign	0.93
DEOGEN2	Benign	0.053	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.044	D;T;D
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.34
MutPred		0.66		Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);
MVP		0.12
MPC		0.026
ClinPred		0.11	T
GERP RS		3.3
Varity_R		0.078
gMVP		0.63

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: rs31517; hg19: chr5-135287029;