chr20-31968290-C-T

Variant names:

• chr20-31968290-C-T
• rs1024502683
• NM_001011718.2:c.115C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001011718.2(XKR7):​c.115C>T​(p.Pro39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,210,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: XKR7 NM_001011718.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0280
• 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: Likely_benign. 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=0.0434815).

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.115C>T	p.Pro39Ser	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.115C>T	p.Pro39Ser	missense	Exon 1 of 3	ENSP00000477059.1	Q5GH72

Frequencies

GnomAD3 genomes AF: 0.0000471 AC: 7 AN: 148708 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000200

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000565 AC: 6 AN: 1061202 Hom.: 0 Cov.: 30 AF XY: 0.00000199 AC XY: 1 AN XY: 502932

African (AFR) AF: 0.0000450 AC: 1 AN: 22202

American (AMR) AF: 0.00 AC: 0 AN: 7830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12972

East Asian (EAS) AF: 0.00 AC: 0 AN: 24784

South Asian (SAS) AF: 0.00 AC: 0 AN: 19914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3058

European-Non Finnish (NFE) AF: 0.00000551 AC: 5 AN: 907870

Other (OTH) AF: 0.00 AC: 0 AN: 41768

GnomAD4 genome AF: 0.0000470 AC: 7 AN: 148816 Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 3 AN XY: 72584

African (AFR) AF: 0.0000972 AC: 4 AN: 41170

American (AMR) AF: 0.000200 AC: 3 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66716

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

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	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.3
DANN	Benign	0.95
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.028
PrimateAI	Pathogenic	0.82	D
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.087
MutPred		0.25		Gain of phosphorylation at P39 (P = 0.0235)
MVP		0.043
ClinPred		0.065	T
GERP RS		-2.2
PromoterAI		-0.072	Neutral
Varity_R		0.019
gMVP		0.12
Mutation Taster		=95/5	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: rs1024502683; hg19: chr20-30556093;