8-6812310-G-C

Position:

• chr8-6812310-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207411.5(XKR5):​c.949C>G​(p.Leu317Val) 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. 8/13 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: 2.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29296505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR5	NM_207411.5	c.949C>G	p.Leu317Val	missense_variant	7/7	ENST00000618742.3	NP_997294.3
XKR5	NM_001289973.2	c.460C>G	p.Leu154Val	missense_variant	8/8		NP_001276902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR5	ENST00000618742.3	c.949C>G	p.Leu317Val	missense_variant	7/7	1	NM_207411.5	ENSP00000483879.1
XKR5	ENST00000618990.4	n.*826C>G		non_coding_transcript_exon_variant	8/8	1		ENSP00000485506.1
XKR5	ENST00000618990.4	n.*826C>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

Sep 29, 2022

The c.949C>G (p.L317V) 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 949, causing the leucine (L) at amino acid position 317 to be replaced by a valine (V). 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	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.63
DEOGEN2	Benign	0.037	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.29	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.030	D
Vest4		0.21
MVP		0.24
GERP RS		3.0
Varity_R		0.036
gMVP		0.27

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: chr8-6669831;