11-114522962-C-A

Variant names:

• chr11-114522962-C-A
• NM_001395504.1:c.1025G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395504.1(NXPE1):​c.1025G>T​(p.Gly342Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NXPE1 NM_001395504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.49
• Publications: 0 publications found

Genes affected

NXPE1 (HGNC:28527): (neurexophilin and PC-esterase domain family member 1) Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NXPE2 (HGNC:26331): (neurexophilin and PC-esterase domain family member 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15322632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395504.1. 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
	NXPE1	NM_001395504.1	MANE Select	c.1025G>T	p.Gly342Val	missense	Exon 8 of 9	NP_001382433.1	Q8N323-1
	NXPE1	NM_001367953.1		c.1025G>T	p.Gly342Val	missense	Exon 7 of 8	NP_001354882.1	Q8N323-1
	NXPE1	NM_152315.5		c.599G>T	p.Gly200Val	missense	Exon 5 of 6	NP_689528.2	Q8N323-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPE1	ENST00000534921.3	TSL:3 MANE Select	c.1025G>T	p.Gly342Val	missense	Exon 8 of 9	ENSP00000439503.2	Q8N323-1
	NXPE1	ENST00000251921.6	TSL:1	c.599G>T	p.Gly200Val	missense	Exon 5 of 6	ENSP00000251921.2	Q8N323-2
	NXPE1	ENST00000536271.5	TSL:1	n.1417G>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.020
DANN	Benign	0.57
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.031
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.0030	B
Vest4		0.27
MutPred		0.48		Loss of catalytic residue at G342 (P = 0.0645)
MVP		0.040
MPC		0.022
ClinPred		0.089	T
GERP RS		-8.2
Varity_R		0.036
gMVP		0.089
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr11-114393684;