1-203216964-CG-TC

Variant names:

• chr1-203216964-CG-TC
• NM_003465.3:c.1325_1326delCGinsGA
• CHIT1 p.Ala442Gly

Variant summary

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

The NM_003465.3(CHIT1):​c.1325_1326delCGinsGA​(p.Ala442Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A442V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHIT1 NM_003465.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 0 publications found

Genes affected

CHIT1 (HGNC:1936): (chitinase 1) Chitotriosidase is secreted by activated human macrophages and is markedly elevated in plasma of Gaucher disease patients. The expression of chitotriosidase occurs only at a late stage of differentiation of monocytes to activated macrophages in culture. Human macrophages can synthesize a functional chitotriosidase, a highly conserved enzyme with a strongly regulated expression. This enzyme may play a role in the degradation of chitin-containing pathogens. Several alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003465.3. 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
	CHIT1	NM_003465.3	MANE Select	c.1325_1326delCGinsGA	p.Ala442Gly	missense	N/A	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.1268_1269delCGinsGA	p.Ala423Gly	missense	N/A	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.1590_1591delCGinsGA		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.1325_1326delCGinsGA	p.Ala442Gly	missense	N/A	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000491855.5	TSL:1	n.*232_*233delCGinsGA		non_coding_transcript_exon	Exon 12 of 12	ENSP00000423778.1	Q13231-2
	CHIT1	ENST00000503786.1	TSL:1	n.*467_*468delCGinsGA		non_coding_transcript_exon	Exon 13 of 13	ENSP00000421617.1	D6REY1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.081

Splicing

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: chr1-203186092;