NM_004000.3:c.318T>A

Variant names:

• chr1-111231283-T-A
• NM_004000.3:c.318T>A
• CHI3L2 p.Phe106Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004000.3(CHI3L2):​c.318T>A​(p.Phe106Leu) 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. 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: 33)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32525805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004000.3. 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
	CHI3L2	NM_004000.3	MANE Select	c.318T>A	p.Phe106Leu	missense	Exon 4 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.288T>A	p.Phe96Leu	missense	Exon 3 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.81T>A	p.Phe27Leu	missense	Exon 3 of 10	NP_001020370.1	Q15782-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.318T>A	p.Phe106Leu	missense	Exon 4 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.81T>A	p.Phe27Leu	missense	Exon 3 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.318T>A	p.Phe106Leu	missense	Exon 6 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.033	D
Varity_R		0.56
gMVP		0.39
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-111773905;