1-27960245-C-T

Variant names:

• chr1-27960245-C-T
• rs932653119
• NM_018053.4:c.176C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018053.4(XKR8):​c.176C>T​(p.Ala59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,372,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A59G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: XKR8 NM_018053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 0 publications found

Genes affected

XKR8 (HGNC:25508): (XK related 8) Enables phospholipid scramblase activity. Involved in engulfment of apoptotic cell; phosphatidylserine exposure on apoptotic cell surface; and positive regulation of myoblast differentiation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000227050 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043275148).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR8	NM_018053.4	MANE Select	c.176C>T	p.Ala59Val	missense	Exon 1 of 3	NP_060523.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR8	ENST00000373884.6	TSL:1 MANE Select	c.176C>T	p.Ala59Val	missense	Exon 1 of 3	ENSP00000362991.5	Q9H6D3
	XKR8	ENST00000675575.1		c.176C>T	p.Ala59Val	missense	Exon 1 of 4	ENSP00000502552.1	A0A6Q8PH47
	XKR8	ENST00000675759.1		c.-101+505C>T		intron	N/A	ENSP00000502285.1	A0A6Q8PGH8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1372962 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 677082

African (AFR) AF: 0.00 AC: 0 AN: 30010

American (AMR) AF: 0.00 AC: 0 AN: 35086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24876

East Asian (EAS) AF: 0.00 AC: 0 AN: 34814

South Asian (SAS) AF: 0.00 AC: 0 AN: 77844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4418

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075104

Other (OTH) AF: 0.00 AC: 0 AN: 57366

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.86
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.34
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.025
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.064	B
Vest4		0.059
MutPred		0.38		Gain of catalytic residue at A59 (P = 0.0691)
MVP		0.22
MPC		0.43
ClinPred		0.051	T
GERP RS		0.015
PromoterAI		-0.040	Neutral
Varity_R		0.042
gMVP		0.063
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs932653119; hg19: chr1-28286756;