NM_004000.3:c.830C>T

Variant names:

• chr1-111238844-C-T
• rs1659962225
• NM_004000.3:c.830C>T

Variant summary

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

The NM_004000.3(CHI3L2):​c.830C>T​(p.Ser277Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• 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=0.4092355).

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.830C>T	p.Ser277Phe	missense	Exon 8 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.800C>T	p.Ser267Phe	missense	Exon 7 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.593C>T	p.Ser198Phe	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.830C>T	p.Ser277Phe	missense	Exon 8 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.593C>T	p.Ser198Phe	missense	Exon 7 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.830C>T	p.Ser277Phe	missense	Exon 10 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727072

African (AFR) AF: 0.000120 AC: 4 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.58		Loss of disorder (P = 0.0045)
MVP		0.61
MPC		0.12
ClinPred		0.99	D
GERP RS		3.4
PromoterAI		0.0082	Neutral
Varity_R		0.77
gMVP		0.29
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1659962225; hg19: chr1-111781466;