rs556640570

Variant names:

• chr11-114698076-T-C
• rs556640570
• NM_182495.6:c.164T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-114698076-T-C
• chr11-114698076-T-G

Variant summary

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

The NM_182495.6(NXPE2):​c.164T>C​(p.Leu55Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,582,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. L55R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NXPE2 NM_182495.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

Genes affected

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

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=0.14287442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPE2	NM_182495.6	c.164T>C	p.Leu55Pro	missense_variant	Exon 3 of 6	ENST00000389586.6	NP_872301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPE2	ENST00000389586.6	c.164T>C	p.Leu55Pro	missense_variant	Exon 3 of 6	5	NM_182495.6	ENSP00000374237.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1429716 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 708496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152378 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74512

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.045
Sift	Benign	0.077	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.65		Loss of stability (P = 0.009);
MVP		0.055
MPC		0.010
ClinPred		0.086	T
GERP RS		-1.5
Varity_R		0.42
gMVP		0.54

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: rs556640570; hg19: chr11-114568798;