3-52786995-AG-GT

Variant names:

• chr3-52786995-AG-GT
• NM_002215.4:c.1784_1785delAGinsGT
• ITIH1 p.Gln595Arg

Variant summary

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

The NM_002215.4(ITIH1):​c.1784_1785delAGinsGT​(p.Gln595Arg) 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITIH1 NM_002215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

ITIH1 (HGNC:6166): (inter-alpha-trypsin inhibitor heavy chain 1) This gene encodes a member of the inter-alpha-trypsin inhibitor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the heavy chain of the inter-alpha-trypsin inhibitor complex, which is secreted by hepatocytes into the blood. The heavy chain also interacts with hyaluronan, and this interaction may play a role in ovulation and fertilization, and has been implicated in multiple inflammatory diseases. This gene is present in a gene cluster on chromosome 3. [provided by RefSeq, Nov 2015]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002215.4. 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
	ITIH1	NM_002215.4	MANE Select	c.1784_1785delAGinsGT	p.Gln595Arg	missense	N/A	NP_002206.2	P19827-1
	ITIH1	NM_001166434.3		c.1358_1359delAGinsGT	p.Gln453Arg	missense	N/A	NP_001159906.1	P19827-2
	ITIH1	NM_001166435.2		c.920_921delAGinsGT	p.Gln307Arg	missense	N/A	NP_001159907.1	P19827-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH1	ENST00000273283.7	TSL:1 MANE Select	c.1784_1785delAGinsGT	p.Gln595Arg	missense	N/A	ENSP00000273283.2	P19827-1
	ITIH1	ENST00000943717.1		c.1784_1785delAGinsGT	p.Gln595Arg	missense	N/A	ENSP00000613776.1
	ITIH1	ENST00000943715.1		c.1784_1785delAGinsGT	p.Gln595Arg	missense	N/A	ENSP00000613774.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

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: chr3-52821011;