11-114571381-A-G

Position:

• chr11-114571381-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375478.4(NXPE4):​c.1192T>C​(p.Tyr398His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,613,528 control chromosomes in the GnomAD database, including 209,998 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.60 (29077 hom., cov: 32)
  • Exomes 𝑓: 0.49 (180921 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.9848303E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPE4	NM_001077639.2	c.1192T>C	p.Tyr398His	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>C	p.Tyr398His	missense_variant	6/6	1	NM_001077639.2	ENSP00000364627	P1
NXPE4	ENST00000424261.6	c.340T>C	p.Tyr114His	missense_variant	6/6	1		ENSP00000401503

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90939 AN: 151942 Hom.: 29018 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.574

GnomAD3 exomes AF: 0.539 AC: 133332 AN: 247188 Hom.: 37432 AF XY: 0.529 AC XY: 71049 AN XY: 134230

Gnomad AFR exome AF: 0.849

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.540

Gnomad EAS exome AF: 0.686

Gnomad SAS exome AF: 0.542

Gnomad FIN exome AF: 0.492

Gnomad NFE exome AF: 0.470

Gnomad OTH exome AF: 0.522

GnomAD4 exome AF: 0.492 AC: 718560 AN: 1461466 Hom.: 180921 Cov.: 47 AF XY: 0.491 AC XY: 356895 AN XY: 726982

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.540

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.599 AC: 91057 AN: 152062 Hom.: 29077 Cov.: 32 AF XY: 0.600 AC XY: 44546 AN XY: 74284

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.576

Alfa AF: 0.501 Hom.: 47824

Bravo AF: 0.613

TwinsUK AF: 0.465 AC: 1725

ALSPAC AF: 0.443 AC: 1708

ESP6500AA AF: 0.837 AC: 3195

ESP6500EA AF: 0.488 AC: 4029

ExAC AF: 0.540 AC: 65273

Asia WGS AF: 0.619 AC: 2153 AN: 3476

EpiCase AF: 0.473

EpiControl AF: 0.473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.16
DEOGEN2	Benign	0.031	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.31	T;T
MetaRNN	Benign	8.0e-7	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.7	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	5.3	N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.14
MPC		0.073
ClinPred		0.0024	T
GERP RS		4.5
Varity_R		0.058
gMVP		0.60

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; COSMIC: COSV64943401;