Variant 8-6815881-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_207411.5(XKR5):c.845C>T(p.Ala282Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000081 in 1,604,144 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

XKR5
NM_207411.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

Variant links:

Genes affected

XKR5 (HGNC:20782): (XK related 5) 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]

XKR5 links:

Genome browser will be placed here

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, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR5	NM_207411.5 linkuse as main transcript	c.845C>T	p.Ala282Val	missense_variant	6/7	ENST00000618742.3	NP_997294.3	Q6UX68-1
XKR5	NM_001289973.2 linkuse as main transcript	c.356C>T	p.Ala119Val	missense_variant	7/8		NP_001276902.1	Q6UX68

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
XKR5	ENST00000618742.3 linkuse as main transcript	c.845C>T	p.Ala282Val	missense_variant	6/7	1	NM_207411.5	ENSP00000483879.1	Q6UX68-1
XKR5	ENST00000618990.4 linkuse as main transcript	n.*722C>T		non_coding_transcript_exon_variant	7/8	1		ENSP00000485506.1	Q6UX68-3
XKR5	ENST00000618990.4 linkuse as main transcript	n.*722C>T		3_prime_UTR_variant	7/8	1		ENSP00000485506.1	Q6UX68-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000858

AC:

AN:

233218

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126028

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:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000826

AC:

AN:

1452040

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

721208

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:

0.00000993

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000826

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, 2023

The c.845C>T (p.A282V) alteration is located in exon 6 (coding exon 6) of the XKR5 gene. This alteration results from a C to T substitution at nucleotide position 845, causing the alanine (A) at amino acid position 282 to be replaced by a valine (V). 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

0.24

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

DANN

Benign

0.63

DEOGEN2

Benign

0.042

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

MetaRNN

Pathogenic

0.79

PrimateAI

Benign

0.44

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.71

MVP

0.41

GERP RS

5.2

Varity_R

0.21

gMVP

0.61

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