7-142954267-G-C

Variant names:

• chr7-142954267-G-C
• NM_000420.3:c.841C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000420.3(KEL):​c.841C>G​(p.Arg281Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/23 in silico tools predict a benign outcome for this variant. 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. R281Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3	c.841C>G	p.Arg281Gly	missense_variant	Exon 8 of 19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.877C>G	p.Arg293Gly	missense_variant	Exon 8 of 19		XP_005250050.1
KEL	XM_047420357.1	c.841C>G	p.Arg281Gly	missense_variant	Exon 8 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7	c.841C>G	p.Arg281Gly	missense_variant	Exon 8 of 19	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000479768.6	n.959C>G		non_coding_transcript_exon_variant	Exon 8 of 11	5
KEL	ENST00000476829.5	c.*77C>G		downstream_gene_variant		3		ENSP00000419889.1
KEL	ENST00000494148.1	n.*19C>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	M
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.25
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.50	P
Vest4		0.37
MutPred		0.64		Loss of MoRF binding (P = 0.056);
MVP		0.66
MPC		0.16
ClinPred		0.42	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-142651354;