chr22-40857206-A-C

Position:

• chr22-40857206-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022098.4(XPNPEP3):​c.25A>C​(p.Lys9Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPNPEP3 NM_022098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

Genes affected

XPNPEP3 (HGNC:28052): (X-prolyl aminopeptidase 3) The protein encoded by this gene belongs to the family of X-pro-aminopeptidases that utilize a metal cofactor, and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. This protein has been shown to localize to the mitochondria of renal cells, and have a role in ciliary function. Mutations in this gene are associated with nephronophthisis-like nephropathy-1. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene, however, expression of some of these isoforms in vivo is not known.[provided by RefSeq, Mar 2011]

XPNPEP3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20494804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPNPEP3	NM_022098.4	c.25A>C	p.Lys9Gln	missense_variant	1/10	ENST00000357137.9	NP_071381.1
XPNPEP3	NM_001204827.2	c.25A>C	p.Lys9Gln	missense_variant	1/3		NP_001191756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPNPEP3	ENST00000357137.9	c.25A>C	p.Lys9Gln	missense_variant	1/10	1	NM_022098.4	ENSP00000349658.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis-like nephropathy 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T;.
Eigen	Benign	0.00084
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.79	N;.
REVEL	Benign	0.17
Sift	Benign	0.12	T;.
Sift4G	Benign	0.23	T;D
Polyphen		0.39	B;.
Vest4		0.41
MutPred		0.20		Loss of ubiquitination at K9 (P = 0.0297);Loss of ubiquitination at K9 (P = 0.0297);
MVP		0.51
MPC		0.16
ClinPred		0.54	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.22
gMVP		0.57

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: chr22-41253210;