dbSNP rs5748648: XKR3:p.Thr143Met (chr22-16799932-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386955.1(XKR3):c.428C>T(p.Thr143Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 1,613,818 control chromosomes in the GnomAD database, including 6,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.11 ( 1282 hom., cov: 32)

Exomes 𝑓: 0.070 ( 4728 hom. )

Consequence

XKR3
NM_001386955.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.319

Publications

17 publications found

Variant links:

Genes affected

XKR3 (HGNC:28778): (XK related 3) XKRX (MIM 300684) and XKR3 are homologs of the Kell blood group precursor XK (MIM 314850), which is a putative membrane transporter and a component of the XK/Kell complex of the Kell blood group system (Calenda et al., 2006 [PubMed 16431037]).[supplied by OMIM, Mar 2008]

XKR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040911734).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR3	NM_001386955.1 link	c.428C>T	p.Thr143Met	missense_variant	Exon 3 of 4	ENST00000684488.1	NP_001373884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR3	ENST00000684488.1 link	c.428C>T	p.Thr143Met	missense_variant	Exon 3 of 4		NM_001386955.1	ENSP00000507478.1		Q5GH77
XKR3	ENST00000331428.5 link	c.428C>T	p.Thr143Met	missense_variant	Exon 3 of 4	1		ENSP00000331704.5		Q5GH77

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16537

AN:

151962

Hom.:

1281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.0694

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0398

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0566

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.0953

AC:

23750

AN:

249330

AF XY:

0.0933

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0443

Gnomad NFE exome

AF:

0.0573

Gnomad OTH exome

AF:

0.0886

GnomAD4 exome

AF:

0.0699

AC:

102241

AN:

1461738

Hom.:

4728

Cov.:

AF XY:

0.0714

AC XY:

51917

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.221

AC:

7409

AN:

33478

American (AMR)

AF:

0.154

AC:

6865

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0531

AC:

1387

AN:

26132

East Asian (EAS)

AF:

0.0940

AC:

3729

AN:

39676

South Asian (SAS)

AF:

0.144

AC:

12388

AN:

86246

European-Finnish (FIN)

AF:

0.0468

AC:

2501

AN:

53418

Middle Eastern (MID)

AF:

0.108

AC:

621

AN:

5766

European-Non Finnish (NFE)

AF:

0.0560

AC:

62287

AN:

1111914

Other (OTH)

AF:

0.0837

AC:

5054

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

5496

10992

16487

21983

27479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2530

5060

7590

10120

12650

<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:

0.109

AC:

16556

AN:

152080

Hom.:

1282

Cov.:

AF XY:

0.108

AC XY:

8016

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.213

AC:

8824

AN:

41464

American (AMR)

AF:

0.114

AC:

1738

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3466

East Asian (EAS)

AF:

0.103

AC:

534

AN:

5186

South Asian (SAS)

AF:

0.143

AC:

687

AN:

4810

European-Finnish (FIN)

AF:

0.0398

AC:

421

AN:

10578

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0566

AC:

3851

AN:

67996

Other (OTH)

AF:

0.104

AC:

218

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

707

1415

2122

2830

3537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0739

Hom.:

2240

Bravo

AF:

0.119

TwinsUK

AF:

0.0618

AC:

229

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.196

AC:

742

ESP6500EA

AF:

0.0569

AC:

470

ExAC

AF:

0.0950

AC:

11486

Asia WGS

AF:

0.130

AC:

451

AN:

3478

EpiCase

AF:

0.0582

EpiControl

AF:

0.0597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.32

PROVEAN

Benign

0.27

REVEL

Benign

0.078

Sift

Benign

0.11

Sift4G

Benign

0.10

Polyphen

0.021

Vest4

0.024

MPC

0.093

ClinPred

0.013

GERP RS

-1.5

Varity_R

0.016

gMVP

0.074

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over