16-72056201-CTT-ATC

Variant names:

• chr16-72056201-CTT-ATC
• NM_005143.5:c.46_48delCTTinsATC
• HP p.Leu16Ile

Variant summary

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

The NM_005143.5(HP):​c.46_48delCTTinsATC​(p.Leu16Ile) 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: 29)
• Consequence: HP NM_005143.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

HP (HGNC:5141): (haptoglobin) This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

ENSG00000310525 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005143.5. 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
	HP	NM_005143.5	MANE Select	c.46_48delCTTinsATC	p.Leu16Ile	missense	N/A	NP_005134.1	P00738-1
	HP	NM_001126102.3		c.46_48delCTTinsATC	p.Leu16Ile	missense	N/A	NP_001119574.1	P00738-2
	HP	NM_001318138.2		c.46_48delCTTinsATC	p.Leu16Ile	missense	N/A	NP_001305067.1	A0A0C4DGL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	ENST00000355906.10	TSL:1 MANE Select	c.46_48delCTTinsATC	p.Leu16Ile	missense	N/A	ENSP00000348170.5	P00738-1
	HP	ENST00000398131.6	TSL:1	c.46_48delCTTinsATC	p.Leu16Ile	missense	N/A	ENSP00000381199.2	P00738-2
	HP	ENST00000565574.5	TSL:1	c.46_48delCTTinsATC	p.Leu16Ile	missense	N/A	ENSP00000454966.1	A0A0C4DGL8

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

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: chr16-72090100;