rs61729057

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000420.3(KEL):ā€‹c.986T>Cā€‹(p.Leu329Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,880 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: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KELNM_000420.3 linkuse as main transcriptc.986T>C p.Leu329Pro missense_variant 9/19 ENST00000355265.7
KELXM_005249993.2 linkuse as main transcriptc.1022T>C p.Leu341Pro missense_variant 9/19
KELXM_047420357.1 linkuse as main transcriptc.986T>C p.Leu329Pro missense_variant 9/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KELENST00000355265.7 linkuse as main transcriptc.986T>C p.Leu329Pro missense_variant 9/191 NM_000420.3 P1
KELENST00000479768.6 linkuse as main transcriptn.1104T>C non_coding_transcript_exon_variant 9/115

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251346
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135832
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461880
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.55
D
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.74
T
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
0.017
D
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Pathogenic
0.70
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.95
P
Vest4
0.53
MutPred
0.63
Gain of relative solvent accessibility (P = 0.0027);
MVP
0.94
MPC
0.47
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.77
gMVP
0.73

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: rs61729057; hg19: chr7-142650982; COSMIC: COSV100787078; COSMIC: COSV100787078; API