8-70680963-A-T

Variant names:

• chr8-70680963-A-T
• rs12681420
• NM_001011720.2:c.-96A>T

Variant summary

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

The NM_001011720.2(XKR9):​c.-96A>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XKR9 NM_001011720.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 21 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: 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 (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR9	NM_001011720.2	c.-96A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 5	ENST00000408926.8	NP_001011720.1
XKR9	NM_001011720.2	c.-96A>T		5_prime_UTR_variant	Exon 3 of 5	ENST00000408926.8	NP_001011720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR9	ENST00000408926.8	c.-96A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 5	1	NM_001011720.2	ENSP00000386141.3
XKR9	ENST00000408926.8	c.-96A>T		5_prime_UTR_variant	Exon 3 of 5	1	NM_001011720.2	ENSP00000386141.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000100 AC: 1 AN: 995284 Hom.: 0 Cov.: 13 AF XY: 0.00000201 AC XY: 1 AN XY: 498586

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23018

American (AMR) AF: 0.00 AC: 0 AN: 24326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17520

East Asian (EAS) AF: 0.00 AC: 0 AN: 36130

South Asian (SAS) AF: 0.00 AC: 0 AN: 57586

European-Finnish (FIN) AF: 0.0000246 AC: 1 AN: 40726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3022

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 748982

Other (OTH) AF: 0.00 AC: 0 AN: 43974

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 16151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		0.18

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: rs12681420; hg19: chr8-71593198;