Variant chr8-70681318-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001011720.2(XKR9):c.260G>A(p.Gly87Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

XKR9
NM_001011720.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

Variant links:

Genes affected

XKR9 (HGNC:20937): (XK related 9) Predicted to enable phospholipid scramblase activity. 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]

XKR9 links:

ENSG00000285579 (HGNC:):

ENSG00000285579 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR9	NM_001011720.2 link	c.260G>A	p.Gly87Glu	missense_variant	3/5	ENST00000408926.8	NP_001011720.1	Q5GH70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR9	ENST00000408926.8 link	c.260G>A	p.Gly87Glu	missense_variant	3/5	1	NM_001011720.2	ENSP00000386141.3		Q5GH70

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249604

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS 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:

0.00000274

AC:

AN:

1459704

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.260G>A (p.G87E) alteration is located in exon 3 (coding exon 1) of the XKR9 gene. This alteration results from a G to A substitution at nucleotide position 260, causing the glycine (G) at amino acid position 87 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.77

.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.94

MutPred

0.91

Loss of MoRF binding (P = 0.0711);Loss of MoRF binding (P = 0.0711);Loss of MoRF binding (P = 0.0711);

MVP

0.87

MPC

0.0056

ClinPred

0.93

GERP RS

3.5

Varity_R

0.97

gMVP

0.83

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over