NM_000420.3:c.2183G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000420.3(KEL):​c.2183G>A​(p.Arg728His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.854
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14593667).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KELNM_000420.3 linkc.2183G>A p.Arg728His missense_variant Exon 19 of 19 ENST00000355265.7 NP_000411.1 P23276A0A077QP03
KELXM_005249993.2 linkc.2219G>A p.Arg740His missense_variant Exon 19 of 19 XP_005250050.1
KELXM_047420357.1 linkc.2072G>A p.Arg691His missense_variant Exon 18 of 18 XP_047276313.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KELENST00000355265.7 linkc.2183G>A p.Arg728His missense_variant Exon 19 of 19 1 NM_000420.3 ENSP00000347409.2 P23276

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251392
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461844
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000542
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000218
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
4.8
DANN
Benign
0.96
DEOGEN2
Uncertain
0.64
D
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.72
T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.28
Sift
Benign
0.16
T
Sift4G
Benign
0.15
T
Polyphen
0.27
B
Vest4
0.14
MVP
0.61
MPC
0.088
ClinPred
0.054
T
GERP RS
-2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.060
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201835469; hg19: chr7-142638355; COSMIC: COSV62333771; COSMIC: COSV62333771; API