8-55102969-G-A

Variant names:

• chr8-55102969-G-A
• NM_052898.2:c.481G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052898.2(XKR4):​c.481G>A​(p.Val161Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: XKR4 NM_052898.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91
• Publications: 0 publications found

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052898.2. 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
	XKR4	NM_052898.2	MANE Select	c.481G>A	p.Val161Met	missense	Exon 1 of 3	NP_443130.1	Q5GH76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	ENST00000327381.7	TSL:1 MANE Select	c.481G>A	p.Val161Met	missense	Exon 1 of 3	ENSP00000328326.5	Q5GH76

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.30
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.20
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.011	D
Polyphen		0.97	D
Vest4		0.62
MutPred		0.36		Loss of catalytic residue at V161 (P = 0.0456)
MVP		0.49
MPC		1.3
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.35
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr8-56015529;