8-6811580-G-C

Position:

• chr8-6811580-G-C

Variant summary

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

The NM_207411.5(XKR5):​c.1679C>G​(p.Pro560Arg) 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. 10/13 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: XKR5 NM_207411.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56

Genes affected

XKR5 (HGNC:20782): (XK related 5) 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=0.07201332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR5	NM_207411.5	c.1679C>G	p.Pro560Arg	missense_variant	7/7	ENST00000618742.3	NP_997294.3
XKR5	NM_001289973.2	c.1190C>G	p.Pro397Arg	missense_variant	8/8		NP_001276902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR5	ENST00000618742.3	c.1679C>G	p.Pro560Arg	missense_variant	7/7	1	NM_207411.5	ENSP00000483879.1
XKR5	ENST00000618990.4	n.*1556C>G		non_coding_transcript_exon_variant	8/8	1		ENSP00000485506.1
XKR5	ENST00000618990.4	n.*1556C>G		3_prime_UTR_variant	8/8	1		ENSP00000485506.1

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

May 31, 2023

The c.1679C>G (p.P560R) alteration is located in exon 7 (coding exon 7) of the XKR5 gene. This alteration results from a C to G substitution at nucleotide position 1679, causing the proline (P) at amino acid position 560 to be replaced by an arginine (R). 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	0.080
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.1
DANN	Benign	0.75
DEOGEN2	Benign	0.022	T
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.072	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.24	T
Vest4		0.035
MVP		0.25
GERP RS		1.2
Varity_R		0.022
gMVP		0.17

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: chr8-6669101;