8-55102876-G-A

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 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

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 Likely_benign. Variant got -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 id is 2534744.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR4	NM_052898.2	c.388G>A	p.Val130Ile	missense_variant	1/3	ENST00000327381.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XKR4	ENST00000327381.7	c.388G>A	p.Val130Ile	missense_variant	1/3	1	NM_052898.2	P1

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

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0062	N
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.36	N;N
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.37	N;.
REVEL	Benign	0.063
Sift	Benign	0.36	T;.
Sift4G	Benign	0.40	T;T
Polyphen		0.0	B;B
Vest4		0.095
MutPred		0.35		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.043
MPC		0.52
ClinPred		0.080	T
GERP RS		-1.7
Varity_R		0.021
gMVP		0.081

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: chr8-56015436; COSMIC: COSV59318154;