8-55102876-G-A

Variant names:

• chr8-55102876-G-A
• rs748261375
• NM_052898.2:c.388G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_052898.2(XKR4):​c.388G>A​(p.Val130Ile) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XKR4 NM_052898.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

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

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=0.13288051).
• BP6: Variant 8-55102876-G-A is Benign according to our data. Variant chr8-55102876-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2534744.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052898.2. 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
	XKR4	NM_052898.2	MANE Select	c.388G>A	p.Val130Ile	missense	Exon 1 of 3	NP_443130.1	Q5GH76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	ENST00000327381.7	TSL:1 MANE Select	c.388G>A	p.Val130Ile	missense	Exon 1 of 3	ENSP00000328326.5	Q5GH76

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459868 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726334

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111916

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.36	N
PhyloP100		0.63
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.063
Sift	Benign	0.36	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.095
MutPred		0.35		Gain of helix (P = 0.132)
MVP		0.043
MPC		0.52
ClinPred		0.080	T
GERP RS		-1.7
PromoterAI		0.014	Neutral
Varity_R		0.021
gMVP		0.081
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: rs748261375; hg19: chr8-56015436; COSMIC: COSV59318154;