Genetic Variant KEL:p.Val302Ala (chr7-142954203-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000420.3(KEL):c.905T>C(p.Val302Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,611,412 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 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: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

7 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0161573).

BS2

High Homozygotes in GnomAdExome4 at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.905T>C	p.Val302Ala	missense_variant	Exon 8 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.941T>C	p.Val314Ala	missense_variant	Exon 8 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.905T>C	p.Val302Ala	missense_variant	Exon 8 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KEL	ENST00000355265.7 link	c.905T>C	p.Val302Ala	missense_variant	Exon 8 of 19	1	NM_000420.3	ENSP00000347409.2	P23276
KEL	ENST00000479768.6 link	n.1023T>C		non_coding_transcript_exon_variant	Exon 8 of 11	5
KEL	ENST00000476829.5 link	c.*141T>C		downstream_gene_variant		3		ENSP00000419889.1	E9PHG0
KEL	ENST00000494148.1 link	n.*83T>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000914

AC:

139

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00112

AC:

279

AN:

248760

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00287

Gnomad NFE exome

AF:

0.00183

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00163

AC:

2373

AN:

1459202

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1102

AN XY:

726000

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00331

AC:

168

AN:

50806

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00190

AC:

2108

AN:

1111958

Other (OTH)

AF:

0.00131

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

135

269

404

538

673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152210

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41542

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00154

AC:

105

AN:

68000

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.000763

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00118

AC:

143

EpiCase

AF:

0.000927

EpiControl

AF:

0.00207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Uncertain

0.49

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.67

M_CAP

Benign

0.053

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.5

PhyloP100

1.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.3

REVEL

Benign

0.20

Sift

Benign

0.075

Sift4G

Benign

0.089

Polyphen

0.0020

Vest4

0.14

MVP

0.58

MPC

0.079

ClinPred

0.024

GERP RS

2.0

Varity_R

0.088

gMVP

0.31

Mutation Taster

=97/3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over