rs150678405

Variant summary

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

The NM_000420.3(KEL):​c.1600G>T​(p.Val534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0000066 ( 0 hom., cov: 33)

Consequence

KEL
NM_000420.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.841
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=0.1663929).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KELNM_000420.3 linkc.1600G>T p.Val534Leu missense_variant Exon 15 of 19 ENST00000355265.7 NP_000411.1 P23276A0A077QP03
KELXM_005249993.2 linkc.1636G>T p.Val546Leu missense_variant Exon 15 of 19 XP_005250050.1
KELXM_047420357.1 linkc.1489G>T p.Val497Leu missense_variant Exon 14 of 18 XP_047276313.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KELENST00000355265.7 linkc.1600G>T p.Val534Leu missense_variant Exon 15 of 19 1 NM_000420.3 ENSP00000347409.2 P23276
KELENST00000465697.1 linkn.461G>T non_coding_transcript_exon_variant Exon 4 of 4 3
KELENST00000470850.1 linkn.65G>T non_coding_transcript_exon_variant Exon 2 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.035
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.083
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.27
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.059
T
Polyphen
0.48
P
Vest4
0.32
MutPred
0.32
Loss of ubiquitination at K533 (P = 0.1062);
MVP
0.79
MPC
0.23
ClinPred
0.41
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.44

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: rs150678405; hg19: chr7-142640676; API