Genetic Variant NM_018053.4:c.86C>T (chr1-27960155-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T29A) has been classified as Likely benign.

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

Publications

5 publications found

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:

ENSG00000227050 (HGNC:):

ENSG00000227050 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3351145.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR8	NM_018053.4	MANE Select	c.86C>T	p.Thr29Ile	missense	Exon 1 of 3	NP_060523.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XKR8	ENST00000373884.6	TSL:1 MANE Select	c.86C>T	p.Thr29Ile	missense	Exon 1 of 3	ENSP00000362991.5	Q9H6D3
XKR8	ENST00000675575.1		c.86C>T	p.Thr29Ile	missense	Exon 1 of 4	ENSP00000502552.1	A0A6Q8PH47
XKR8	ENST00000675759.1		c.-101+415C>T		intron	N/A	ENSP00000502285.1	A0A6Q8PGH8

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

GnomAD2 exomes

AF:

0.00170

AC:

210

AN:

123880

AF XY:

0.00159

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 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

African (AFR)

AF:

0.000266

AC:

AN:

30066

American (AMR)

AF:

0.000652

AC:

AN:

35276

Ashkenazi Jewish (ASJ)

AF:

0.000401

AC:

AN:

24910

East Asian (EAS)

AF:

0.00

AC:

AN:

35054

South Asian (SAS)

AF:

0.000141

AC:

AN:

78056

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

33550

Middle Eastern (MID)

AF:

0.000413

AC:

AN:

4846

European-Non Finnish (NFE)

AF:

0.00386

AC:

4155

AN:

1076442

Other (OTH)

AF:

0.00264

AC:

152

AN:

57484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

276

553

829

1106

1382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152328

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41584

American (AMR)

AF:

0.000588

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00423

AC:

288

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

XKR8-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

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

PhyloP100

2.1

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

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.21

gMVP

0.30

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over