rs767893228

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000420.3(KEL):​c.1720G>T​(p.Ala574Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

2
11
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KELNM_000420.3 linkc.1720G>T p.Ala574Ser missense_variant Exon 16 of 19 ENST00000355265.7 NP_000411.1 P23276A0A077QP03
KELXM_005249993.2 linkc.1756G>T p.Ala586Ser missense_variant Exon 16 of 19 XP_005250050.1
KELXM_047420357.1 linkc.1609G>T p.Ala537Ser missense_variant Exon 15 of 18 XP_047276313.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KELENST00000355265.7 linkc.1720G>T p.Ala574Ser missense_variant Exon 16 of 19 1 NM_000420.3 ENSP00000347409.2 P23276
KELENST00000470850.1 linkn.168+159G>T intron_variant Intron 2 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250738
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135538
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461782
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.79
T
M_CAP
Uncertain
0.26
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Uncertain
0.25
D
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.63
Sift
Uncertain
0.0060
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.96
D
Vest4
0.58
MutPred
0.75
Loss of sheet (P = 0.0817);
MVP
0.89
MPC
0.37
ClinPred
0.88
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.22
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs767893228; hg19: chr7-142640414; API