Variant 20-31996592-G-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_001011718.2(XKR7):c.875G>A(p.Arg292Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,547,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

XKR7
NM_001011718.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

XKR7 (HGNC:23062): (XK related 7) 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]

XKR7 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=0.05440411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR7	NM_001011718.2 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	3/3	ENST00000562532.3	NP_001011718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR7	ENST00000562532.3 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	3/3	1	NM_001011718.2	ENSP00000477059	P1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

200394

Hom.:

AF XY:

0.000195

AC XY:

AN XY:

107466

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000358

Gnomad OTH exome

AF:

0.000212

GnomAD4 exome

AF:

0.000374

AC:

522

AN:

1395862

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

238

AN XY:

688122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000963

Gnomad4 AMR exome

AF:

0.0000292

Gnomad4 ASJ exome

AF:

0.0000451

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.000461

Gnomad4 OTH exome

AF:

0.000313

GnomAD4 genome

AF:

0.000237

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000340

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000198

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

Aug 04, 2021

The c.875G>A (p.R292Q) alteration is located in exon 3 (coding exon 3) of the XKR7 gene. This alteration results from a G to A substitution at nucleotide position 875, causing the arginine (R) at amino acid position 292 to be replaced by a glutamine (Q). 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

0.068

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0027

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.81

M_CAP

Benign

0.022

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.98

PrimateAI

Benign

0.41

Sift4G

Benign

0.23

Polyphen

0.91

Vest4

0.057

MVP

0.043

ClinPred

0.11

GERP RS

5.0

Varity_R

0.11

gMVP

0.41

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