8-6815861-C-A

Position:

• chr8-6815861-C-A

Variant summary

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

The NM_207411.5(XKR5):​c.865G>T​(p.Ala289Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: XKR5 NM_207411.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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=0.22789761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR5	NM_207411.5	c.865G>T	p.Ala289Ser	missense_variant	6/7	ENST00000618742.3	NP_997294.3
XKR5	NM_001289973.2	c.376G>T	p.Ala126Ser	missense_variant	7/8		NP_001276902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR5	ENST00000618742.3	c.865G>T	p.Ala289Ser	missense_variant	6/7	1	NM_207411.5	ENSP00000483879.1
XKR5	ENST00000618990.4	n.*742G>T		non_coding_transcript_exon_variant	7/8	1		ENSP00000485506.1
XKR5	ENST00000618990.4	n.*742G>T		3_prime_UTR_variant	7/8	1		ENSP00000485506.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453444 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jun 01, 2023

The c.865G>T (p.A289S) alteration is located in exon 6 (coding exon 6) of the XKR5 gene. This alteration results from a G to T substitution at nucleotide position 865, causing the alanine (A) at amino acid position 289 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	0.083
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	9.8
DANN	Benign	0.81
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.23	T
PrimateAI	Benign	0.24	T
Sift4G	Uncertain	0.024	D
Polyphen		0.61	P
Vest4		0.39
MVP		0.25
GERP RS		2.3
Varity_R		0.031
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-6673383;