20-31968549-C-G

Variant names:

• chr20-31968549-C-G
• rs1185379589
• NM_001011718.2:c.374C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001011718.2(XKR7):​c.374C>G​(p.Pro125Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XKR7 NM_001011718.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

Genes affected

XKR7 (HGNC:23062): (XK related 7) 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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.5684 (below the threshold of 3.09). Trascript score misZ: 0.16037 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.20964733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011718.2. 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
	XKR7	NM_001011718.2	MANE Select	c.374C>G	p.Pro125Arg	missense	Exon 1 of 3	NP_001011718.1	Q5GH72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR7	ENST00000562532.3	TSL:1 MANE Select	c.374C>G	p.Pro125Arg	missense	Exon 1 of 3	ENSP00000477059.1	Q5GH72

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.094
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0042	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.0
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.041	D
Polyphen		0.97	D
Vest4		0.16
MutPred		0.50		Loss of glycosylation at P125 (P = 0.043)
MVP		0.043
ClinPred		0.90	D
GERP RS		4.0
PromoterAI		-0.037	Neutral
Varity_R		0.21
gMVP		0.24
Mutation Taster		=87/13	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: rs1185379589; hg19: chr20-30556352;