chr8-55523851-G-A

Position:

• chr8-55523851-G-A

Variant summary

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

The NM_052898.2(XKR4):​c.1577G>A​(p.Cys526Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XKR4 NM_052898.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in 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=0.2560879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR4	NM_052898.2	c.1577G>A	p.Cys526Tyr	missense_variant	3/3	ENST00000327381.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XKR4	ENST00000327381.7	c.1577G>A	p.Cys526Tyr	missense_variant	3/3	1	NM_052898.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 14, 2023

The c.1577G>A (p.C526Y) alteration is located in exon 3 (coding exon 3) of the XKR4 gene. This alteration results from a G to A substitution at nucleotide position 1577, causing the cysteine (C) at amino acid position 526 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	0.20
BayesDel_addAF	Benign	-0.0035	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	0.033
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.8	D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.037	D;D
Polyphen		0.011	B;B
Vest4		0.54
MutPred		0.28		Gain of phosphorylation at C526 (P = 0.0248);Gain of phosphorylation at C526 (P = 0.0248);
MVP		0.39
MPC		1.7
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.52
gMVP		0.86

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: chr8-56436410;