chr8-10898179-G-T

Position:

• chr8-10898179-G-T

Variant summary

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

The NM_173683.4(XKR6):​c.1699C>A​(p.Pro567Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XKR6 NM_173683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

Genes affected

XKR6 (HGNC:27806): (XK related 6) 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=0.17285022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR6	NM_173683.4	c.1699C>A	p.Pro567Thr	missense_variant	3/3	ENST00000416569.3	NP_775954.2
XKR6	XM_024447129.2	c.1798C>A	p.Pro600Thr	missense_variant	3/3		XP_024302897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR6	ENST00000416569.3	c.1699C>A	p.Pro567Thr	missense_variant	3/3	1	NM_173683.4	ENSP00000416707.2
XKR6	ENST00000382461.8	c.922C>A	p.Pro308Thr	missense_variant	3/3	1		ENSP00000371900.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jul 30, 2024

The c.1699C>A (p.P567T) alteration is located in exon 3 (coding exon 3) of the XKR6 gene. This alteration results from a C to A substitution at nucleotide position 1699, causing the proline (P) at amino acid position 567 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.38
Sift	Benign	0.048	D
Sift4G	Benign	0.063	T
Polyphen		0.28	B
Vest4		0.091
MutPred		0.34		Gain of glycosylation at P567 (P = 0.0323);
MVP		0.22
MPC		0.24
ClinPred		0.88	D
GERP RS		4.7
Varity_R		0.34
gMVP		0.39

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: rs1799939965; hg19: chr8-10755689;