Variant rs61729034 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000355265.7(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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

KEL
ENST00000355265.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein
KEL	NM_000420.3 linkuse as main transcript	c.905T>C	p.Val302Ala	missense_variant	8/19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2 linkuse as main transcript	c.941T>C	p.Val314Ala	missense_variant	8/19		XP_005250050.1
KEL	XM_047420357.1 linkuse as main transcript	c.905T>C	p.Val302Ala	missense_variant	8/18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7 linkuse as main transcript	c.905T>C	p.Val302Ala	missense_variant	8/19	1	NM_000420.3	ENSP00000347409	P1
KEL	ENST00000479768.6 linkuse as main transcript	n.1023T>C		non_coding_transcript_exon_variant	8/11	5

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

GnomAD3 exomes

AF:

0.00112

AC:

279

AN:

248760

Hom.:

AF XY:

0.00121

AC XY:

163

AN XY:

134668

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00190

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152210

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00130

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

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

MutationTaster

Benign

1.0

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

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