rs8176058

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000420.3(KEL):c.578C>T(p.Thr193Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,614,034 control chromosomes in the GnomAD database, including 1,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 70 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1116 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.00

Publications

38 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013251543).

BP6

Variant 7-142957921-G-A is Benign according to our data. Variant chr7-142957921-G-A is described in ClinVar as Benign. ClinVar VariationId is 17722.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0261 (3968/152230) while in subpopulation NFE AF = 0.0414 (2818/68010). AF 95% confidence interval is 0.0402. There are 70 homozygotes in GnomAd4. There are 1791 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 70 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.578C>T	p.Thr193Met	missense_variant	Exon 6 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.614C>T	p.Thr205Met	missense_variant	Exon 6 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.578C>T	p.Thr193Met	missense_variant	Exon 6 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7 link	c.578C>T	p.Thr193Met	missense_variant	Exon 6 of 19	1	NM_000420.3	ENSP00000347409.2		P23276

Frequencies

GnomAD3 genomes

AF:

0.0261

AC:

3972

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00886

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0567

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.0269

AC:

6762

AN:

251390

AF XY:

0.0278

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0583

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0332

GnomAD4 exome

AF:

0.0366

AC:

53573

AN:

1461804

Hom.:

1116

Cov.:

AF XY:

0.0362

AC XY:

26330

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00815

AC:

273

AN:

33478

American (AMR)

AF:

0.0157

AC:

703

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

1573

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0131

AC:

1128

AN:

86254

European-Finnish (FIN)

AF:

0.0195

AC:

1044

AN:

53416

Middle Eastern (MID)

AF:

0.0496

AC:

286

AN:

5766

European-Non Finnish (NFE)

AF:

0.0418

AC:

46432

AN:

1111940

Other (OTH)

AF:

0.0353

AC:

2130

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2871

5743

8614

11486

14357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1688

3376

5064

6752

8440

<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:

0.0261

AC:

3968

AN:

152230

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1791

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00881

AC:

366

AN:

41526

American (AMR)

AF:

0.0190

AC:

291

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0567

AC:

197

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00954

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0184

AC:

195

AN:

10620

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0414

AC:

2818

AN:

68010

Other (OTH)

AF:

0.0204

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

203

406

608

811

1014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0379

Hom.:

261

Bravo

AF:

0.0264

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0402

AC:

155

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.0414

AC:

356

ExAC

AF:

0.0274

AC:

3325

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0408

EpiControl

AF:

0.0413

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KELL K/k BLOOD GROUP POLYMORPHISM

Benign:1

Jun 01, 1996

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.67

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.6

PhyloP100

3.0

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.22

Sift

Benign

0.039

Sift4G

Uncertain

0.049

Polyphen

0.96

Vest4

0.085

MPC

0.39

ClinPred

0.028

GERP RS

4.0

Varity_R

0.11

gMVP

0.58

Mutation Taster

=99/1

polymorphism (auto)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over