Variant 8-70733838-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001011720.2(XKR9):c.536C>G(p.Thr179Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 1,598,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

XKR9
NM_001011720.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3127488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR9	NM_001011720.2 linkuse as main transcript	c.536C>G	p.Thr179Ser	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.536C>G	p.Thr179Ser	missense_variant	5/5	1	NM_001011720.2	ENSP00000386141	P1
XKR9	ENST00000520030.5 linkuse as main transcript	c.536C>G	p.Thr179Ser	missense_variant	6/6	1		ENSP00000431088	P1
XKR9	ENST00000520092.5 linkuse as main transcript	c.*276C>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000430781
XKR9	ENST00000520273.1 linkuse as main transcript	n.352+26685C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000380

AC:

AN:

237022

Hom.:

AF XY:

0.00000782

AC XY:

AN XY:

127918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000225

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

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:

0.00000622

AC:

AN:

1446034

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718510

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Apr 18, 2024

The c.536C>G (p.T179S) alteration is located in exon 5 (coding exon 3) of the XKR9 gene. This alteration results from a C to G substitution at nucleotide position 536, causing the threonine (T) at amino acid position 179 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

Benign

0.30

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.045

D;D

Polyphen

0.99

D;D

Vest4

0.34

MutPred

0.64

Loss of glycosylation at T179 (P = 0.0987);Loss of glycosylation at T179 (P = 0.0987);

MVP

0.77

MPC

0.0070

ClinPred

0.34

GERP RS

4.7

Varity_R

0.59

gMVP

0.27

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