8-70706999-C-G

Variant names:

• chr8-70706999-C-G
• rs747314955
• NM_001011720.2:c.339C>G

Variant summary

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

The NM_001287258.2(XKR9):​c.-58C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: XKR9 NM_001287258.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 0 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=0.083836526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287258.2. 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.339C>G	p.Phe113Leu	missense	Exon 4 of 5	NP_001011720.1	Q5GH70
	XKR9	NM_001287258.2		c.-58C>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 6	NP_001274187.1
	XKR9	NM_001287259.2		c.339C>G	p.Phe113Leu	missense	Exon 5 of 6	NP_001274188.1	Q5GH70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR9	ENST00000408926.8	TSL:1 MANE Select	c.339C>G	p.Phe113Leu	missense	Exon 4 of 5	ENSP00000386141.3	Q5GH70
	XKR9	ENST00000520030.5	TSL:1	c.339C>G	p.Phe113Leu	missense	Exon 5 of 6	ENSP00000431088.1	Q5GH70
	XKR9	ENST00000920915.1		c.339C>G	p.Phe113Leu	missense	Exon 4 of 5	ENSP00000590974.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461086 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111470

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.0
DANN	Benign	0.73
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.23
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.070
Sift	Benign	0.74	T
Sift4G	Benign	0.83	T
Polyphen		0.065	B
Vest4		0.17
MutPred		0.58		Loss of helix (P = 0.0626)
MVP		0.040
MPC		0.0020
ClinPred		0.061	T
GERP RS		0.83
Varity_R		0.047
gMVP		0.21
Mutation Taster		=98/2	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: rs747314955; hg19: chr8-71619234;