rs550897

Variant names:

• chr11-114571381-A-C
• rs550897
• NM_001077639.2:c.1192T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001077639.2(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. 13/22 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: NXPE4 NM_001077639.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43
• Publications: 35 publications found

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: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=0.15228608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077639.2. 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
	NXPE4	NM_001077639.2	MANE Select	c.1192T>G	p.Tyr398Asp	missense	Exon 6 of 6	NP_001071107.1	Q6UWF7-1
	NXPE4	NM_017678.3		c.340T>G	p.Tyr114Asp	missense	Exon 6 of 6	NP_060148.2	Q6UWF7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPE4	ENST00000375478.4	TSL:1 MANE Select	c.1192T>G	p.Tyr398Asp	missense	Exon 6 of 6	ENSP00000364627.3	Q6UWF7-1
	NXPE4	ENST00000424261.6	TSL:1	c.340T>G	p.Tyr114Asp	missense	Exon 6 of 6	ENSP00000401503.2	Q6UWF7-2
	NXPE4	ENST00000873921.1		c.1252T>G	p.Tyr418Asp	missense	Exon 7 of 7	ENSP00000543980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 72353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.042	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
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: rs550897; hg19: chr11-114442103;