rs374738603

Variant names:

• chr1-27960311-C-A
• rs374738603
• NM_018053.4:c.242C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-27960311-C-A
• chr1-27960311-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018053.4(XKR8):​c.242C>A​(p.Pro81Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,434,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P81L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: XKR8 NM_018053.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345
• Publications: 0 publications found

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]

ENSG00000227050 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0042926967).

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>A	p.Pro81Gln	missense	Exon 1 of 3	NP_060523.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR8	ENST00000373884.6	TSL:1 MANE Select	c.242C>A	p.Pro81Gln	missense	Exon 1 of 3	ENSP00000362991.5	Q9H6D3
	XKR8	ENST00000675575.1		c.242C>A	p.Pro81Gln	missense	Exon 1 of 4	ENSP00000502552.1	A0A6Q8PH47
	XKR8	ENST00000675759.1		c.-101+571C>A		intron	N/A	ENSP00000502285.1	A0A6Q8PGH8

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.0000441 AC: 2 AN: 45306 AF XY: 0.00

Gnomad AFR exome AF: 0.000779

Gnomad AMR exome AF: 0.000120

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: 0.00000312 AC: 4 AN: 1282750 Hom.: 0 Cov.: 31 AF XY: 0.00000318 AC XY: 2 AN XY: 628156

African (AFR) AF: 0.0000783 AC: 2 AN: 25550

American (AMR) AF: 0.0000510 AC: 1 AN: 19612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19002

East Asian (EAS) AF: 0.00 AC: 0 AN: 31052

South Asian (SAS) AF: 0.00 AC: 0 AN: 64574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31124

Middle Eastern (MID) AF: 0.000228 AC: 1 AN: 4390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1034202

Other (OTH) AF: 0.00 AC: 0 AN: 53244

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74374

African (AFR) AF: 0.0000724 AC: 3 AN: 41454

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.000282 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000208 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.34
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.14
Sift	Benign	0.057	T
Sift4G	Uncertain	0.059	T
Polyphen		0.18	B
Vest4		0.077
MVP		0.16
MPC		0.42
ClinPred		0.042	T
GERP RS		4.0
PromoterAI		-0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.069
gMVP		0.12
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs374738603; hg19: chr1-28286822;