NM_000420.3:c.539_540delGCinsAT

Variant names:

• chr7-142957959-GC-AT
• NM_000420.3:c.539_540delGCinsAT
• KEL p.Arg180His

Variant summary

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

The NM_000420.3(KEL):​c.539_540delGCinsAT​(p.Arg180His) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R180C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 0 publications found

Genes affected

KEL (HGNC:6308): (Kell metallo-endopeptidase (Kell blood group)) This gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases. [provided by RefSeq, Jul 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000420.3. 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
	KEL	NM_000420.3	MANE Select	c.539_540delGCinsAT	p.Arg180His	missense	N/A	NP_000411.1	A0A077QP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KEL	ENST00000355265.7	TSL:1 MANE Select	c.539_540delGCinsAT	p.Arg180His	missense	N/A	ENSP00000347409.2	P23276
	KEL	ENST00000949853.1		c.539_540delGCinsAT	p.Arg180His	missense	N/A	ENSP00000619912.1
	KEL	ENST00000476829.5	TSL:3	c.525+344_525+345delGCinsAT		intron	N/A	ENSP00000419889.1	E9PHG0

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		-0.33

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: chr7-142655046;