NM_001011720.2:c.479C>A

Variant names:

• chr8-70707139-C-A
• rs200806311
• NM_001011720.2:c.479C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001011720.2(XKR9):​c.479C>A​(p.Ala160Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A160V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XKR9 NM_001011720.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907
• Publications: 3 publications found

Genes affected

XKR9 (HGNC:20937): (XK related 9) Predicted to enable phospholipid scramblase activity. Predicted to be involved in apoptotic process involved in development; engulfment of apoptotic cell; and 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]

ENSG00000285579 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25623193).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011720.2. 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
	XKR9	NM_001011720.2	MANE Select	c.479C>A	p.Ala160Glu	missense	Exon 4 of 5	NP_001011720.1	Q5GH70
	XKR9	NM_001287259.2		c.479C>A	p.Ala160Glu	missense	Exon 5 of 6	NP_001274188.1	Q5GH70
	XKR9	NM_001287260.2		c.479C>A	p.Ala160Glu	missense	Exon 4 of 5	NP_001274189.1	Q5GH70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR9	ENST00000408926.8	TSL:1 MANE Select	c.479C>A	p.Ala160Glu	missense	Exon 4 of 5	ENSP00000386141.3	Q5GH70
	XKR9	ENST00000520030.5	TSL:1	c.479C>A	p.Ala160Glu	missense	Exon 5 of 6	ENSP00000431088.1	Q5GH70
	XKR9	ENST00000920915.1		c.479C>A	p.Ala160Glu	missense	Exon 4 of 5	ENSP00000590974.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.7
DANN	Benign	0.87
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.91
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.20
Sift	Benign	0.51	T
Sift4G	Benign	0.46	T
Polyphen		0.83	P
Vest4		0.28
MutPred		0.72		Gain of solvent accessibility (P = 0.0068)
MVP		0.52
MPC		0.0021
ClinPred		0.35	T
GERP RS		-2.5
Varity_R		0.20
gMVP		0.33
Mutation Taster		=96/4	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: rs200806311; hg19: chr8-71619374;