Variant 8-70706933-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001011720.2(XKR9):c.273G>T(p.Arg91Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,607,428 control chromosomes in the GnomAD database, including 2 homozygotes. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

XKR9
NM_001011720.2 missense, splice_region

Scores

Splicing: ADA: 0.9769

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 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.273G>T	p.Arg91Ser	missense_variant, splice_region_variant	4/5	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.273G>T	p.Arg91Ser	missense_variant, splice_region_variant	4/5	1	NM_001011720.2	ENSP00000386141	P1
XKR9	ENST00000520030.5 linkuse as main transcript	c.273G>T	p.Arg91Ser	missense_variant, splice_region_variant	5/6	1		ENSP00000431088	P1
XKR9	ENST00000520273.1 linkuse as main transcript	n.132G>T		splice_region_variant, non_coding_transcript_exon_variant	2/4	3
XKR9	ENST00000520092.5 linkuse as main transcript	c.*13G>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	5/6	2		ENSP00000430781

Frequencies

GnomAD3 genomes

AF:

0.000770

AC:

117

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000490

AC:

122

AN:

249130

Hom.:

AF XY:

0.000423

AC XY:

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000328

Gnomad NFE exome

AF:

0.000913

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.00118

AC:

1711

AN:

1455272

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

829

AN XY:

724228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000301

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.000382

GnomAD4 genome

AF:

0.000769

AC:

117

AN:

152156

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000767

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000470

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

Sep 16, 2021

The c.273G>T (p.R91S) alteration is located in exon 4 (coding exon 2) of the XKR9 gene. This alteration results from a G to T substitution at nucleotide position 273, causing the arginine (R) at amino acid position 91 to be replaced by a serine (S). 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

0.96

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

.;T

M_CAP

Uncertain

0.092

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.91

MutPred

0.94

Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);

MVP

0.89

MPC

0.0063

ClinPred

0.12

GERP RS

4.4

Varity_R

0.97

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.84

SpliceAI score (max)

0.060

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