Variant 20-31968245-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001011718.2(XKR7):c.70C>T(p.Arg24Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,139,958 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 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

XKR7
NM_001011718.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23072502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR7	NM_001011718.2 linkuse as main transcript	c.70C>T	p.Arg24Trp	missense_variant	1/3	ENST00000562532.3	NP_001011718.1	Q5GH72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR7	ENST00000562532.3 linkuse as main transcript	c.70C>T	p.Arg24Trp	missense_variant	1/3	1	NM_001011718.2	ENSP00000477059.1		Q5GH72

Frequencies

GnomAD3 genomes

AF:

0.000174

AC:

AN:

149788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00153

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

990170

Hom.:

Cov.:

AF XY:

0.00000858

AC XY:

AN XY:

466240

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000906

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:

0.00

Gnomad4 OTH exome

AF:

0.0000538

GnomAD4 genome

AF:

0.000174

AC:

AN:

149788

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

AN XY:

73050

show subpopulations

Gnomad4 AFR

AF:

0.0000730

Gnomad4 AMR

AF:

0.00153

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000525

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

Nov 19, 2024

The c.70C>T (p.R24W) alteration is located in exon 1 (coding exon 1) of the XKR7 gene. This alteration results from a C to T substitution at nucleotide position 70, causing the arginine (R) at amino acid position 24 to be replaced by a tryptophan (W). 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

0.33

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.94

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.25

MutPred

0.29

Loss of solvent accessibility (P = 0.0079);

MVP

0.043

ClinPred

0.84

GERP RS

2.7

Varity_R

0.27

gMVP

0.19

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