rs8176038
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000420.3(KEL):c.1790T>C(p.Leu597Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,614,116 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.025 ( 165 hom., cov: 33)
Exomes 𝑓: 0.0029 ( 147 hom. )
Consequence
KEL
NM_000420.3 missense
NM_000420.3 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.569
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0025378764).
BP6
?
Variant 7-142943026-A-G is Benign according to our data. Variant chr7-142943026-A-G is described in ClinVar as [Benign]. Clinvar id is 31082.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KEL | NM_000420.3 | c.1790T>C | p.Leu597Pro | missense_variant | 17/19 | ENST00000355265.7 | |
KEL | XM_005249993.2 | c.1826T>C | p.Leu609Pro | missense_variant | 17/19 | ||
KEL | XM_047420357.1 | c.1679T>C | p.Leu560Pro | missense_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KEL | ENST00000355265.7 | c.1790T>C | p.Leu597Pro | missense_variant | 17/19 | 1 | NM_000420.3 | P1 | |
KEL | ENST00000478969.1 | n.129T>C | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
KEL | ENST00000470850.1 | n.169-79T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0250 AC: 3811AN: 152170Hom.: 164 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00674 AC: 1694AN: 251394Hom.: 67 AF XY: 0.00475 AC XY: 646AN XY: 135898
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GnomAD4 exome AF: 0.00288 AC: 4217AN: 1461830Hom.: 147 Cov.: 33 AF XY: 0.00255 AC XY: 1855AN XY: 727218
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GnomAD4 genome ? AF: 0.0251 AC: 3816AN: 152286Hom.: 165 Cov.: 33 AF XY: 0.0242 AC XY: 1802AN XY: 74462
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ESP6500AA
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383
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Kel6 antigen Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 15, 2003 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 04, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at