Variant 8-70707018-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001011720.2(XKR9):c.358C>A(p.Leu120Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

XKR9
NM_001011720.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.38

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048793018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR9	NM_001011720.2 linkuse as main transcript	c.358C>A	p.Leu120Ile	missense_variant	4/5	ENST00000408926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
XKR9	ENST00000408926.8 linkuse as main transcript	c.358C>A	p.Leu120Ile	missense_variant	4/5	1	NM_001011720.2	P1
XKR9	ENST00000520030.5 linkuse as main transcript	c.358C>A	p.Leu120Ile	missense_variant	5/6	1		P1
XKR9	ENST00000520273.1 linkuse as main transcript	n.217C>A		non_coding_transcript_exon_variant	2/4	3
XKR9	ENST00000520092.5 linkuse as main transcript	c.*98C>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251068

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461174

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

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

Dec 03, 2021

The c.358C>A (p.L120I) alteration is located in exon 4 (coding exon 2) of the XKR9 gene. This alteration results from a C to A substitution at nucleotide position 358, causing the leucine (L) at amino acid position 120 to be replaced by an isoleucine (I). 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

Benign

0.067

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.5

DANN

Benign

0.91

DEOGEN2

Benign

0.00061

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.0016

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.080

N;N

REVEL

Benign

0.12

Sift

Benign

0.42

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0020

B;B

Vest4

0.15

MutPred

0.55

Gain of methylation at K122 (P = 0.0506);Gain of methylation at K122 (P = 0.0506);

MVP

0.16

MPC

0.0021

ClinPred

0.042

GERP RS

1.9

Varity_R

0.046

gMVP

0.040

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