Genetic Variant NM_018053.4:c.242C>T (chr1-27960311-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018053.4(XKR8):c.242C>T(p.Pro81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,434,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

XKR8
NM_018053.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.345

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052901328).

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.242C>T	p.Pro81Leu	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.242C>T	p.Pro81Leu	missense	Exon 1 of 3	ENSP00000362991.5	Q9H6D3
XKR8	ENST00000675575.1		c.242C>T	p.Pro81Leu	missense	Exon 1 of 4	ENSP00000502552.1	A0A6Q8PH47
XKR8	ENST00000675759.1		c.-101+571C>T		intron	N/A	ENSP00000502285.1	A0A6Q8PGH8

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD2 exomes

AF:

0.0000221

AC:

AN:

45306

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000779

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1282750

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

628156

show subpopulations

African (AFR)

AF:

0.000705

AC:

AN:

25550

American (AMR)

AF:

0.00

AC:

AN:

19612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19002

East Asian (EAS)

AF:

0.00

AC:

AN:

31052

South Asian (SAS)

AF:

0.00

AC:

AN:

64574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4390

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1034202

Other (OTH)

AF:

0.0000376

AC:

AN:

53244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000204

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000724

AC:

AN:

41454

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000104

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.56

M_CAP

Benign

0.028

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.0

PhyloP100

0.34

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.66

REVEL

Benign

0.16

Sift

Benign

0.052

Sift4G

Uncertain

0.050

Polyphen

0.17

Vest4

0.064

MutPred

0.57

Loss of catalytic residue at P80 (P = 0.0131)

MVP

0.17

MPC

0.44

ClinPred

0.53

GERP RS

4.0

PromoterAI

0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.072

gMVP

0.17

Mutation Taster

=96/4

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