chr8-6821982-C-A

Position:

• chr8-6821982-C-A

Variant summary

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

The NM_207411.5(XKR5):​c.694G>T​(p.Asp232Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: XKR5 NM_207411.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR5	NM_207411.5	c.694G>T	p.Asp232Tyr	missense_variant	5/7	ENST00000618742.3	NP_997294.3
XKR5	NM_001289973.2	c.205G>T	p.Asp69Tyr	missense_variant	6/8		NP_001276902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR5	ENST00000618742.3	c.694G>T	p.Asp232Tyr	missense_variant	5/7	1	NM_207411.5	ENSP00000483879.1
XKR5	ENST00000618990.4	n.*571G>T		non_coding_transcript_exon_variant	6/8	1		ENSP00000485506.1
XKR5	ENST00000618990.4	n.*571G>T		3_prime_UTR_variant	6/8	1		ENSP00000485506.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454726 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Dec 16, 2023

The c.694G>T (p.D232Y) alteration is located in exon 5 (coding exon 5) of the XKR5 gene. This alteration results from a G to T substitution at nucleotide position 694, causing the aspartic acid (D) at amino acid position 232 to be replaced by a tyrosine (Y). 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	0.17
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.76
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.71	T
MetaRNN	Uncertain	0.62	D
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.040	D
Polyphen		0.89	P
Vest4		0.59
MVP		0.29
GERP RS		3.9
Varity_R		0.099
gMVP		0.46

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: chr8-6679504;