Variant 8-70707091-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001011720.2(XKR9):c.431G>A(p.Cys144Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,232 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

XKR9
NM_001011720.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR9	NM_001011720.2 linkuse as main transcript	c.431G>A	p.Cys144Tyr	missense_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.431G>A	p.Cys144Tyr	missense_variant	4/5	1	NM_001011720.2	ENSP00000386141	P1
XKR9	ENST00000520030.5 linkuse as main transcript	c.431G>A	p.Cys144Tyr	missense_variant	5/6	1		ENSP00000431088	P1
XKR9	ENST00000520273.1 linkuse as main transcript	n.290G>A		non_coding_transcript_exon_variant	2/4	3
XKR9	ENST00000520092.5 linkuse as main transcript	c.*171G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	2		ENSP00000430781

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

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

Jan 09, 2024

The c.431G>A (p.C144Y) alteration is located in exon 4 (coding exon 2) of the XKR9 gene. This alteration results from a G to A substitution at nucleotide position 431, causing the cysteine (C) at amino acid position 144 to be replaced by a tyrosine (Y). 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

0.68

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.83

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

0.98

D;D

Vest4

0.55

MutPred

0.81

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);

MVP

0.81

MPC

0.0039

ClinPred

0.95

GERP RS

3.4

Varity_R

0.56

gMVP

0.55

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