Variant 2-190519150-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142645.2(NEMP2):c.247G>A(p.Val83Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,549,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

NEMP2
NM_001142645.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

NEMP2 (HGNC:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

NEMP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014719039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEMP2	NM_001142645.2 linkuse as main transcript	c.247G>A	p.Val83Ile	missense_variant	3/9	ENST00000409150.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEMP2	ENST00000409150.8 linkuse as main transcript	c.247G>A	p.Val83Ile	missense_variant	3/9	2	NM_001142645.2	P1	A6NFY4-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000179

AC:

AN:

156556

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

82822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000125

AC:

175

AN:

1397614

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

689514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000989

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.0000688

GnomAD4 genome

AF:

0.000151

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000224

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000238

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.247G>A (p.V83I) alteration is located in exon 3 (coding exon 3) of the NEMP2 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the valine (V) at amino acid position 83 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.52

Cadd

Benign

5.0

Dann

Benign

0.94

DEOGEN2

Benign

0.0081

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.096

Sift

Benign

0.21

T;.

Sift4G

Benign

0.084

T;.

Polyphen

0.91

P;.

Vest4

0.097

MVP

0.13

ClinPred

0.044

GERP RS

2.6

Varity_R

0.019

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over