rs12681420

Positions:

• chr8-70680963-A-G
• chr8-70680963-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001011720.2(XKR9):​c.-96A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,144,236 control chromosomes in the GnomAD database, including 87,573 homozygotes. 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: 𝑓 0.33 (9415 hom., cov: 32)
  • Exomes 𝑓: 0.38 (78158 hom.)
• Consequence: XKR9 NM_001011720.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR9	NM_001011720.2	c.-96A>G		5_prime_UTR_variant	3/5	ENST00000408926.8	NP_001011720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR9	ENST00000408926.8	c.-96A>G		5_prime_UTR_variant	3/5	1	NM_001011720.2	ENSP00000386141	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50166 AN: 151832 Hom.: 9413 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.384 AC: 380617 AN: 992286 Hom.: 78158 Cov.: 13 AF XY: 0.379 AC XY: 188380 AN XY: 497198

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.349

GnomAD4 genome AF: 0.330 AC: 50175 AN: 151950 Hom.: 9415 Cov.: 32 AF XY: 0.328 AC XY: 24372 AN XY: 74250

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0613

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.335

Alfa AF: 0.402 Hom.: 12433

Bravo AF: 0.309

Asia WGS AF: 0.134 AC: 467 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs12681420; hg19: chr8-71593198;