8-6811303-C-G

Position:

• chr8-6811303-C-G

Variant summary

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

The NM_207411.5(XKR5):​c.1956G>C​(p.Arg652Ser) 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. 9/13 in silico tools predict 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: 33)
• Consequence: XKR5 NM_207411.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.212

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=0.11388853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR5	NM_207411.5	c.1956G>C	p.Arg652Ser	missense_variant	7/7	ENST00000618742.3	NP_997294.3
XKR5	NM_001289973.2	c.1467G>C	p.Arg489Ser	missense_variant	8/8		NP_001276902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR5	ENST00000618742.3	c.1956G>C	p.Arg652Ser	missense_variant	7/7	1	NM_207411.5	ENSP00000483879.1
XKR5	ENST00000618990.4	n.*1833G>C		non_coding_transcript_exon_variant	8/8	1		ENSP00000485506.1
XKR5	ENST00000618990.4	n.*1833G>C		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

Aug 11, 2024

The c.1956G>C (p.R652S) alteration is located in exon 7 (coding exon 7) of the XKR5 gene. This alteration results from a G to C substitution at nucleotide position 1956, causing the arginine (R) at amino acid position 652 to be replaced by a serine (S). 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	0.26
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	9.3
DANN	Benign	0.45
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.11	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.25	T
Sift4G	Uncertain	0.057	T
Vest4		0.080
MVP		0.41
GERP RS		-3.9
Varity_R		0.098
gMVP		0.32

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: chr8-6668824;