chr7-142941386-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000420.3(KEL):c.2065G>T(p.Asp689Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,606,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 0.893

Publications

3 publications found

Variant links:

COSMIC-nc: COSV62335755

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17483234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.2065G>T	p.Asp689Tyr	missense_variant	Exon 19 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.2101G>T	p.Asp701Tyr	missense_variant	Exon 19 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.1954G>T	p.Asp652Tyr	missense_variant	Exon 18 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7 link	c.2065G>T	p.Asp689Tyr	missense_variant	Exon 19 of 19	1	NM_000420.3	ENSP00000347409.2		P23276

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000643

AC:

AN:

248868

AF XY:

0.0000744

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000192

AC:

279

AN:

1454726

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

136

AN XY:

722268

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33354

American (AMR)

AF:

0.0000225

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.00

AC:

AN:

85958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.000246

AC:

272

AN:

1106666

Other (OTH)

AF:

0.0000832

AC:

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151960

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41352

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2065G>T (p.D689Y) alteration is located in exon 19 (coding exon 19) of the KEL gene. This alteration results from a G to T substitution at nucleotide position 2065, causing the aspartic acid (D) at amino acid position 689 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Other:1

Feb 10, 2020

Australian Red Cross Blood Service

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:research

The patient, this variant was found in, showed discrepant KEL:2 results between different antisera used. some antisera was KEL:2 negative and some was weakly KEL:2 positive. Patient was heterozygous for the antithetical allele KEL:1. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.52

M_CAP

Benign

0.066

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.58

PhyloP100

0.89

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.29

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0030

Polyphen

0.045

Vest4

0.39

MVP

0.71

MPC

0.18

ClinPred

0.072

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.46

Mutation Taster

=78/22

polymorphism

(source)

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

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chr7-142941386-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over