Variant chr12-57069252-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130963.2(NEMP1):c.527G>A(p.Cys176Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,394,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

NEMP1
NM_001130963.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88

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:

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ACMG classification

Classification made for transcript

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=0.16473037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEMP1	NM_001130963.2 linkuse as main transcript	c.527G>A	p.Cys176Tyr	missense_variant	4/9	ENST00000300128.9	NP_001124435.1	O14524-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEMP1	ENST00000300128.9 linkuse as main transcript	c.527G>A	p.Cys176Tyr	missense_variant	4/9	1	NM_001130963.2	ENSP00000300128.4	O14524-1
NEMP1	ENST00000379391.7 linkuse as main transcript	c.326+1568G>A		intron_variant		1		ENSP00000368701.3	O14524-2
NEMP1	ENST00000554340.1 linkuse as main transcript	n.*48G>A		non_coding_transcript_exon_variant	4/8	1		ENSP00000452391.1	G3V5K2
NEMP1	ENST00000554340.1 linkuse as main transcript	n.*48G>A		3_prime_UTR_variant	4/8	1		ENSP00000452391.1	G3V5K2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1394726

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

687802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000195

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

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

Oct 05, 2023

The c.527G>A (p.C176Y) alteration is located in exon 4 (coding exon 4) of the NEMP1 gene. This alteration results from a G to A substitution at nucleotide position 527, causing the cysteine (C) at amino acid position 176 to be replaced by a tyrosine (Y). 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

0.24

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.83

M_CAP

Benign

0.0079

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.1

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.12

Vest4

0.40

MutPred

0.72

Gain of sheet (P = 0.1208);

MVP

0.50

MPC

1.1

ClinPred

0.64

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.81

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