Variant 1-27960155-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018053.4(XKR8):c.86C>T(p.Thr29Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,528,012 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 16 hom. )

Consequence

XKR8
NM_018053.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

XKR8 (HGNC:25508): (XK related 8) Enables phospholipid scramblase activity. Involved in engulfment of apoptotic cell; phosphatidylserine exposure on apoptotic cell surface; and positive regulation of myoblast differentiation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

XKR8 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0110657215).

BP6

Variant 1-27960155-C-T is Benign according to our data. Variant chr1-27960155-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3351145.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR8	NM_018053.4 linkuse as main transcript	c.86C>T	p.Thr29Ile	missense_variant	1/3	ENST00000373884.6	NP_060523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR8	ENST00000373884.6 linkuse as main transcript	c.86C>T	p.Thr29Ile	missense_variant	1/3	1	NM_018053.4	ENSP00000362991	P1
	ENST00000448015.1 linkuse as main transcript	n.34+5G>A		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00170

AC:

210

AN:

123880

Hom.:

AF XY:

0.00159

AC XY:

108

AN XY:

67918

show subpopulations

Gnomad AFR exome

AF:

0.000213

Gnomad AMR exome

AF:

0.000422

Gnomad ASJ exome

AF:

0.000381

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000937

Gnomad FIN exome

AF:

0.000929

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00320

AC:

4400

AN:

1375684

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

2172

AN XY:

678784

show subpopulations

Gnomad4 AFR exome

AF:

0.000266

Gnomad4 AMR exome

AF:

0.000652

Gnomad4 ASJ exome

AF:

0.000401

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00386

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152328

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000281

AC:

ESP6500EA

AF:

0.00164

AC:

ExAC

AF:

0.000634

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XKR8-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 26, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.59

M_CAP

Benign

0.037

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.74

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

REVEL

Benign

0.097

Sift

Benign

0.081

Sift4G

Uncertain

0.0040

Polyphen

0.0050

Vest4

0.11

MVP

0.44

MPC

0.48

ClinPred

0.059

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.21

gMVP

0.30

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