8-10898139-G-A

Position:

• chr8-10898139-G-A

Variant summary

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

The NM_173683.4(XKR6):​c.1739C>T​(p.Pro580Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.80

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR6	NM_173683.4	c.1739C>T	p.Pro580Leu	missense_variant	3/3	ENST00000416569.3
XKR6	XM_024447129.2	c.1838C>T	p.Pro613Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XKR6	ENST00000416569.3	c.1739C>T	p.Pro580Leu	missense_variant	3/3	1	NM_173683.4	P1
XKR6	ENST00000382461.8	c.962C>T	p.Pro321Leu	missense_variant	3/3	1

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

Mar 04, 2024

The c.1739C>T (p.P580L) alteration is located in exon 3 (coding exon 3) of the XKR6 gene. This alteration results from a C to T substitution at nucleotide position 1739, causing the proline (P) at amino acid position 580 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.37
Sift	Benign	0.56	T
Sift4G	Benign	0.40	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.31		Loss of disorder (P = 0.016);
MVP		0.47
MPC		0.81
ClinPred		0.70	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.45

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: rs1799938300; hg19: chr8-10755649;