rs61729041

Variant names:

• chr7-142946304-C-G
• rs61729041
• NM_000420.3:c.1217G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-142946304-C-G
• chr7-142946304-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000420.3(KEL):​c.1217G>C​(p.Arg406Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3	c.1217G>C	p.Arg406Pro	missense_variant	Exon 11 of 19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.1253G>C	p.Arg418Pro	missense_variant	Exon 11 of 19		XP_005250050.1
KEL	XM_047420357.1	c.1204-1563G>C		intron_variant	Intron 10 of 17		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7	c.1217G>C	p.Arg406Pro	missense_variant	Exon 11 of 19	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000479768.6	n.1626G>C		non_coding_transcript_exon_variant	Exon 11 of 11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.7
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.78		Gain of glycosylation at R406 (P = 0.0144);
MVP		0.82
MPC		0.45
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.80
gMVP		0.89
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs61729041; hg19: chr7-142643391;