Genetic Variant XKR4:p.Glu47Lys (chr8-55102627-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052898.2(XKR4):c.139G>A(p.Glu47Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000351 in 1,394,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

XKR4
NM_052898.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107

Publications

1 publications found

Variant links:

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in phosphatidylserine exposure on apoptotic cell surface. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

XKR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016918272).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052898.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	NM_052898.2	MANE Select	c.139G>A	p.Glu47Lys	missense	Exon 1 of 3	NP_443130.1	Q5GH76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	ENST00000327381.7	TSL:1 MANE Select	c.139G>A	p.Glu47Lys	missense	Exon 1 of 3	ENSP00000328326.5	Q5GH76

Frequencies

GnomAD3 genomes

AF:

0.000173

AC:

AN:

150310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000606

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000586

AC:

AN:

153458

AF XY:

0.0000460

show subpopulations

Gnomad AFR exome

AF:

0.000882

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1244560

Hom.:

Cov.:

AF XY:

0.0000164

AC XY:

AN XY:

610170

show subpopulations

African (AFR)

AF:

0.000718

AC:

AN:

26472

American (AMR)

AF:

0.0000727

AC:

AN:

27492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19644

East Asian (EAS)

AF:

0.00

AC:

AN:

30268

South Asian (SAS)

AF:

0.0000194

AC:

AN:

51424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4686

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

992410

Other (OTH)

AF:

0.00

AC:

AN:

49080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000173

AC:

AN:

150418

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73530

show subpopulations

African (AFR)

AF:

0.000604

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67522

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000356

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000459

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000750

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.0

PhyloP100

0.11

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.010

REVEL

Benign

0.24

Sift

Benign

0.84

Sift4G

Benign

0.27

Polyphen

0.16

Vest4

0.22

MVP

0.28

MPC

0.72

ClinPred

0.024

GERP RS

1.5

PromoterAI

0.029

Neutral

(source)

Varity_R

0.033

gMVP

0.25

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over