Variant rs751310423 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000420.3(KEL):c.2005C>G(p.Pro669Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,455,448 control chromosomes in the GnomAD database, including 1 homozygotes. 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: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

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]

KEL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40685776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.2005C>G	p.Pro669Ala	missense_variant	Exon 18 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.2041C>G	p.Pro681Ala	missense_variant	Exon 18 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.1894C>G	p.Pro632Ala	missense_variant	Exon 17 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KEL	ENST00000355265.7 link	c.2005C>G	p.Pro669Ala	missense_variant	Exon 18 of 19	1	NM_000420.3	ENSP00000347409.2	P23276
KEL	ENST00000470850.1 link	n.305C>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
KEL	ENST00000478969.1 link	n.344C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000209

AC:

AN:

239108

Hom.:

AF XY:

0.00000776

AC XY:

AN XY:

128934

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:

0.000174

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1455448

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723160

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:

0.000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.39

Eigen

Benign

-0.025

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.78

M_CAP

Benign

0.061

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.27

Sift

Benign

0.066

Sift4G

Benign

0.28

Polyphen

0.45

Vest4

0.46

MutPred

0.59

Loss of disorder (P = 0.0942);

MVP

0.97

MPC

0.19

ClinPred

0.40

GERP RS

3.4

Varity_R

0.095

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over