rs550897

Positions:

• chr11-114571381-A-C
• chr11-114571381-A-G
• chr11-114571381-A-T

Variant summary

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

The ENST00000375478.4(NXPE4):​c.1192T>G​(p.Tyr398Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y398H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NXPE4 ENST00000375478.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

Genes affected

NXPE4 (HGNC:23117): (neurexophilin and PC-esterase domain family member 4) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

NXPE2 (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=0.15228608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPE4	NM_001077639.2	c.1192T>G	p.Tyr398Asp	missense_variant	6/6	ENST00000375478.4	NP_001071107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXPE4	ENST00000375478.4	c.1192T>G	p.Tyr398Asp	missense_variant	6/6	1	NM_001077639.2	ENSP00000364627	P1
NXPE4	ENST00000424261.6	c.340T>G	p.Tyr114Asp	missense_variant	6/6	1		ENSP00000401503

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.1	D;N
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		0.071	.;B
Vest4		0.23
MutPred		0.64		.;Gain of relative solvent accessibility (P = 0.0166);
MVP		0.12
MPC		0.10
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.34
gMVP		0.71

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

LitVar

Other links and lift over

dbSNP: rs550897; hg19: chr11-114442103;