Genetic Variant XKR6:p.Glu29Lys (chr8-11201255-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173683.4(XKR6):c.85G>A(p.Glu29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,567,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E29Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

XKR6
NM_173683.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.934

Publications

0 publications found

Variant links:

Genes affected

XKR6 (HGNC:27806): (XK related 6) Predicted to be involved in apoptotic process involved in development; engulfment of apoptotic cell; and 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]

XKR6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13171577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR6	NM_173683.4 link	c.85G>A	p.Glu29Lys	missense_variant	Exon 1 of 3	ENST00000416569.3	NP_775954.2	Q5GH73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR6	ENST00000416569.3 link	c.85G>A	p.Glu29Lys	missense_variant	Exon 1 of 3	1	NM_173683.4	ENSP00000416707.2		Q5GH73-1
XKR6	ENST00000297303.4 link	c.85G>A	p.Glu29Lys	missense_variant	Exon 1 of 2	1		ENSP00000297303.4		Q96KT3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000108

AC:

AN:

184772

AF XY:

0.00000967

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000322

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:

0.00000212

AC:

AN:

1416488

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

703146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31194

American (AMR)

AF:

0.0000239

AC:

AN:

41766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25150

East Asian (EAS)

AF:

0.00

AC:

AN:

36858

South Asian (SAS)

AF:

0.0000245

AC:

AN:

81758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100022

Other (OTH)

AF:

0.00

AC:

AN:

58808

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

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151270

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73868

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41204

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67628

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000885

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.90

L;.

PhyloP100

0.93

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.17

Sift

Benign

0.19

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0010

B;.

Vest4

0.27

MutPred

0.27

Gain of ubiquitination at E29 (P = 0.0104);Gain of ubiquitination at E29 (P = 0.0104);

MVP

0.11

MPC

1.2

ClinPred

0.12

GERP RS

1.8

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.15

gMVP

0.30

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over