8-70707011-A-C

Position:

• chr8-70707011-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001011720.2(XKR9):​c.351A>C​(p.Gln117His) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: XKR9 NM_001011720.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1439957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR9	NM_001011720.2	c.351A>C	p.Gln117His	missense_variant	4/5	ENST00000408926.8	NP_001011720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR9	ENST00000408926.8	c.351A>C	p.Gln117His	missense_variant	4/5	1	NM_001011720.2	ENSP00000386141	P1
XKR9	ENST00000520030.5	c.351A>C	p.Gln117His	missense_variant	5/6	1		ENSP00000431088	P1
XKR9	ENST00000520273.1	n.210A>C		non_coding_transcript_exon_variant	2/4	3
XKR9	ENST00000520092.5	c.*91A>C		3_prime_UTR_variant, NMD_transcript_variant	5/6	2		ENSP00000430781

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2023

The c.351A>C (p.Q117H) alteration is located in exon 4 (coding exon 2) of the XKR9 gene. This alteration results from a A to C substitution at nucleotide position 351, causing the glutamine (Q) at amino acid position 117 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.9
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.63	N;N
REVEL	Benign	0.15
Sift	Benign	0.11	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.96	D;D
Vest4		0.21
MutPred		0.42		Gain of disorder (P = 0.1017);Gain of disorder (P = 0.1017);
MVP		0.12
MPC		0.0024
ClinPred		0.19	T
GERP RS		3.0
Varity_R		0.054
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-71619246;