Variant 12-57059916-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001130963.2(NEMP1):c.1298G>A(p.Arg433Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,613,772 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 18 hom. )

Consequence

NEMP1
NM_001130963.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.91

Variant links:

Genes affected

NEMP1 (HGNC:29001): (nuclear envelope integral membrane protein 1) Involved in nuclear membrane organization. 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]

NEMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003554076).

BP6

Variant 12-57059916-C-T is Benign according to our data. Variant chr12-57059916-C-T is described in ClinVar as [Benign]. Clinvar id is 789050.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEMP1	NM_001130963.2 linkuse as main transcript	c.1298G>A	p.Arg433Gln	missense_variant	9/9	ENST00000300128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEMP1	ENST00000300128.9 linkuse as main transcript	c.1298G>A	p.Arg433Gln	missense_variant	9/9	1	NM_001130963.2	P1	O14524-1
NEMP1	ENST00000379391.7 linkuse as main transcript	c.1079G>A	p.Arg360Gln	missense_variant	8/8	1			O14524-2
NEMP1	ENST00000554340.1 linkuse as main transcript	c.*704G>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	1

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

616

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00366

AC:

918

AN:

250898

Hom.:

AF XY:

0.00364

AC XY:

494

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.00462

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00275

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.00238

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00312

AC:

4559

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2265

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00418

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.0184

Gnomad4 NFE exome

AF:

0.00262

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00405

AC:

616

AN:

152124

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

368

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00460

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00268

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00354

AC:

430

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.85

Cadd

Benign

0.0060

Dann

Benign

0.41

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.0070

Sift

Benign

0.63

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0010

B;B

Vest4

0.078

MVP

0.12

MPC

0.33

ClinPred

0.0023

GERP RS

-9.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.0084

gMVP

0.15

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