chr15-80879742-GAG-AAA

Variant names:

• chr15-80879742-GAG-AAA
• NM_001293298.2:c.268_270delGAGinsAAA
• CEMIP p.Glu90Lys

Variant summary

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

The NM_001293298.2(CEMIP):​c.268_270delGAGinsAAA​(p.Glu90Lys) 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: 33)
• Consequence: CEMIP NM_001293298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

CEMIP (HGNC:29213): (cell migration inducing hyaluronidase 1) Enables several functions, including clathrin heavy chain binding activity; hyaluronic acid binding activity; and hyalurononglucosaminidase activity. Involved in several processes, including hyaluronan catabolic process; positive regulation of protein phosphorylation; and positive regulation of transport. Located in clathrin-coated endocytic vesicle; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEMIP Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001293298.2. 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
	CEMIP	NM_001293298.2	MANE Select	c.268_270delGAGinsAAA	p.Glu90Lys	missense	N/A	NP_001280227.1	Q8WUJ3-1
	CEMIP	NM_001293304.2		c.268_270delGAGinsAAA	p.Glu90Lys	missense	N/A	NP_001280233.1	Q8WUJ3-1
	CEMIP	NM_018689.3		c.268_270delGAGinsAAA	p.Glu90Lys	missense	N/A	NP_061159.1	Q8WUJ3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	ENST00000394685.8	TSL:1 MANE Select	c.268_270delGAGinsAAA	p.Glu90Lys	missense	N/A	ENSP00000378177.3	Q8WUJ3-1
	CEMIP	ENST00000220244.7	TSL:1	c.268_270delGAGinsAAA	p.Glu90Lys	missense	N/A	ENSP00000220244.3	Q8WUJ3-1
	CEMIP	ENST00000356249.9	TSL:1	c.268_270delGAGinsAAA	p.Glu90Lys	missense	N/A	ENSP00000348583.5	Q8WUJ3-1

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		2.7

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: chr15-81172083;