Variant 12-57060937-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001130963.2(NEMP1):c.989G>C(p.Cys330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,608 control chromosomes in the GnomAD database, including 33 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 0.0084 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 17 hom. )

Consequence

NEMP1
NM_001130963.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00200

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040560663).

BP6

Variant 12-57060937-C-G is Benign according to our data. Variant chr12-57060937-C-G is described in ClinVar as [Benign]. Clinvar id is 787099.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00837 (1274/152276) while in subpopulation AFR AF= 0.0292 (1214/41544). AF 95% confidence interval is 0.0279. There are 16 homozygotes in gnomad4. There are 584 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEMP1	NM_001130963.2 linkuse as main transcript	c.989G>C	p.Cys330Ser	missense_variant	8/9	ENST00000300128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEMP1	ENST00000300128.9 linkuse as main transcript	c.989G>C	p.Cys330Ser	missense_variant	8/9	1	NM_001130963.2	P1	O14524-1
NEMP1	ENST00000379391.7 linkuse as main transcript	c.770G>C	p.Cys257Ser	missense_variant	7/8	1			O14524-2
NEMP1	ENST00000554340.1 linkuse as main transcript	c.*395G>C		3_prime_UTR_variant, NMD_transcript_variant	7/8	1

Frequencies

GnomAD3 genomes

AF:

0.00833

AC:

1267

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

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:

0.000118

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00210

AC:

527

AN:

250644

Hom.:

AF XY:

0.00143

AC XY:

194

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000857

AC:

1253

AN:

1461332

Hom.:

Cov.:

AF XY:

0.000710

AC XY:

516

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.0310

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00837

AC:

1274

AN:

152276

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

584

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00954

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0270

AC:

119

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00283

AC:

344

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.60

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.022

Sift

Benign

0.41

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.47

P;B

Vest4

0.49

MutPred

0.38

.;Gain of disorder (P = 0.0064);

MVP

0.32

MPC

0.45

ClinPred

0.0022

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.24

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