7-142941365-G-C

Variant summary

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

The NM_000420.3(KEL):ā€‹c.2086C>Gā€‹(p.Pro696Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,454 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‘“: 6.9e-7 ( 0 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.41
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, 0.936

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KELNM_000420.3 linkc.2086C>G p.Pro696Ala missense_variant Exon 19 of 19 ENST00000355265.7 NP_000411.1 P23276A0A077QP03
KELXM_005249993.2 linkc.2122C>G p.Pro708Ala missense_variant Exon 19 of 19 XP_005250050.1
KELXM_047420357.1 linkc.1975C>G p.Pro659Ala 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.2086C>G p.Pro696Ala missense_variant Exon 19 of 19 1 NM_000420.3 ENSP00000347409.2 P23276

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459454
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725466
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000279
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.77
D
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.77
T
M_CAP
Pathogenic
0.29
D
MetaRNN
Pathogenic
0.94
D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Pathogenic
3.7
H
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-7.0
D
REVEL
Uncertain
0.56
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.45
MutPred
0.84
Loss of glycosylation at T693 (P = 0.0679);
MVP
0.98
MPC
0.37
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.41
gMVP
0.49

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: rs758657888; hg19: chr7-142638452; API