Variant 8-70733901-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001011720.2(XKR9):c.599G>A(p.Cys200Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,612,530 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 25 hom. )

Consequence

XKR9
NM_001011720.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.222

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007441044).

BP6

Variant 8-70733901-G-A is Benign according to our data. Variant chr8-70733901-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658646.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR9	NM_001011720.2 linkuse as main transcript	c.599G>A	p.Cys200Tyr	missense_variant	5/5	ENST00000408926.8	NP_001011720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
XKR9	ENST00000408926.8 linkuse as main transcript	c.599G>A	p.Cys200Tyr	missense_variant	5/5	1	NM_001011720.2	ENSP00000386141	P1
XKR9	ENST00000520030.5 linkuse as main transcript	c.599G>A	p.Cys200Tyr	missense_variant	6/6	1		ENSP00000431088	P1
XKR9	ENST00000520092.5 linkuse as main transcript	c.*339G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000430781
XKR9	ENST00000520273.1 linkuse as main transcript	n.352+26748G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

494

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00699

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00313

AC:

783

AN:

249884

Hom.:

AF XY:

0.00303

AC XY:

409

AN XY:

134964

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.00648

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.00574

GnomAD4 exome

AF:

0.00512

AC:

7481

AN:

1460362

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

3590

AN XY:

726306

show subpopulations

Gnomad4 AFR exome

AF:

0.000837

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.00650

Gnomad4 NFE exome

AF:

0.00588

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.00324

AC:

493

AN:

152168

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00699

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00278

AC:

338

Asia WGS

AF:

0.00116

AC:

AN:

3472

EpiCase

AF:

0.00595

EpiControl

AF:

0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

XKR9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.0

DANN

Benign

0.20

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.51

N;N

REVEL

Benign

0.049

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.22

B;B

Vest4

0.075

MVP

0.44

MPC

0.0016

ClinPred

0.015

GERP RS

1.6

Varity_R

0.092

gMVP

0.35

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