dbSNP rs9605146: XKR3:p.Pro232Leu (chr22-16784304-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.695C>T(p.Pro232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,668 control chromosomes in the GnomAD database, including 117,528 homozygotes. 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 0.39 ( 11783 hom., cov: 33)

Exomes 𝑓: 0.38 ( 105745 hom. )

Consequence

XKR3
NM_001386955.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

29 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=0.0059199333).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR3	NM_001386955.1 link	c.695C>T	p.Pro232Leu	missense_variant	Exon 4 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.695C>T	p.Pro232Leu	missense_variant	Exon 4 of 4		NM_001386955.1	ENSP00000507478.1		Q5GH77
XKR3	ENST00000331428.5 link	c.695C>T	p.Pro232Leu	missense_variant	Exon 4 of 4	1		ENSP00000331704.5		Q5GH77

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

59021

AN:

151930

Hom.:

11782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.378

AC:

551915

AN:

1461620

Hom.:

105745

Cov.:

AF XY:

0.378

AC XY:

274702

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.454

AC:

15200

AN:

33478

American (AMR)

AF:

0.220

AC:

9821

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

11532

AN:

26130

East Asian (EAS)

AF:

0.425

AC:

16874

AN:

39700

South Asian (SAS)

AF:

0.382

AC:

32911

AN:

86242

European-Finnish (FIN)

AF:

0.275

AC:

14697

AN:

53408

Middle Eastern (MID)

AF:

0.422

AC:

2435

AN:

5768

European-Non Finnish (NFE)

AF:

0.382

AC:

424674

AN:

1111794

Other (OTH)

AF:

0.394

AC:

23771

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

19665

39331

58996

78662

98327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13472

26944

40416

53888

67360

<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:

0.388

AC:

59050

AN:

152048

Hom.:

11783

Cov.:

AF XY:

0.383

AC XY:

28477

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.447

AC:

18524

AN:

41462

American (AMR)

AF:

0.323

AC:

4926

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1549

AN:

3472

East Asian (EAS)

AF:

0.447

AC:

2304

AN:

5156

South Asian (SAS)

AF:

0.398

AC:

1917

AN:

4822

European-Finnish (FIN)

AF:

0.264

AC:

2784

AN:

10562

Middle Eastern (MID)

AF:

0.497

AC:

145

AN:

292

European-Non Finnish (NFE)

AF:

0.378

AC:

25724

AN:

67986

Other (OTH)

AF:

0.399

AC:

845

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1846

3692

5539

7385

9231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.389

Hom.:

34421

Bravo

AF:

0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.4

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.16

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.38

M_CAP

Benign

0.0037

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.6

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.14

Sift

Benign

0.39

Sift4G

Uncertain

0.053

Polyphen

0.33

Vest4

0.17

MVP

0.23

MPC

3.3

ClinPred

0.25

GERP RS

-0.57

Varity_R

0.063

gMVP

0.19

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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