Variant chr7-142944337-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000420.3(KEL):c.1477C>A(p.Gln493Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.907

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:

KEL (HGNC:):

KEL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015610009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KEL	NM_000420.3 linkuse as main transcript	c.1477C>A	p.Gln493Lys	missense_variant	13/19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 linkuse as main transcript	c.1513C>A	p.Gln505Lys	missense_variant	13/19		XP_005250050.1
KEL	XM_047420357.1 linkuse as main transcript	c.1366C>A	p.Gln456Lys	missense_variant	12/18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7 linkuse as main transcript	c.1477C>A	p.Gln493Lys	missense_variant	13/19	1	NM_000420.3	ENSP00000347409.2		P23276
KEL	ENST00000465697.1 linkuse as main transcript	n.338C>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251476

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135908

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:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461544

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727114

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:

0.00

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000144

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000164

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.22

CADD

Benign

7.2

DANN

Benign

0.73

DEOGEN2

Benign

0.078

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.72

M_CAP

Benign

0.033

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.50

REVEL

Benign

0.23

Sift

Benign

0.94

Sift4G

Benign

0.15

Polyphen

0.031

Vest4

0.45

MutPred

0.45

Gain of ubiquitination at Q493 (P = 0.0203);

MVP

0.76

MPC

0.086

ClinPred

0.050

GERP RS

3.0

Varity_R

0.043

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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