1-111238804-A-C

Variant names:

• chr1-111238804-A-C
• NM_004000.3:c.790A>C
• CHI3L2 p.Met264Leu

Variant summary

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

The NM_004000.3(CHI3L2):​c.790A>C​(p.Met264Leu) 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. 16/22 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: 32)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24974644).

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.790A>C	p.Met264Leu	missense	Exon 8 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.760A>C	p.Met254Leu	missense	Exon 7 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.553A>C	p.Met185Leu	missense	Exon 7 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.790A>C	p.Met264Leu	missense	Exon 8 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.553A>C	p.Met185Leu	missense	Exon 7 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.790A>C	p.Met264Leu	missense	Exon 10 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-0.31	N
PhyloP100		0.22
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.098
Sift	Benign	0.42	T
Sift4G	Benign	0.61	T
PromoterAI		-0.0094	Neutral
Varity_R		0.24
gMVP		0.37
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr1-111781426;