Genetic Variant NUP42:p.Val395Gly (chr7-23200657-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007342.3(NUP42):c.1184T>G(p.Val395Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

NUP42
NM_007342.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.323

Publications

0 publications found

Variant links:

Genes affected

NUP42 (HGNC:17010): (nucleoporin 42) Enables nuclear export signal receptor activity. Involved in protein export from nucleus. Located in cytosol and nucleoplasm. Colocalizes with nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

NUP42 links:

ENSG00000285926 (HGNC:):

ENSG00000285926 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022226691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP42	NM_007342.3 link	c.1184T>G	p.Val395Gly	missense_variant	Exon 7 of 7	ENST00000258742.10	NP_031368.1	O15504-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP42	ENST00000258742.10 link	c.1184T>G	p.Val395Gly	missense_variant	Exon 7 of 7	1	NM_007342.3	ENSP00000258742.5		O15504-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1184T>G (p.V395G) alteration is located in exon 7 (coding exon 7) of the NUPL2 gene. This alteration results from a T to G substitution at nucleotide position 1184, causing the valine (V) at amino acid position 395 to be replaced by a glycine (G). 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

0.070

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PhyloP100

-0.32

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.030

Sift

Benign

0.40

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.022

B;.

Vest4

0.14

MutPred

0.27

Gain of disorder (P = 0.0492);.;

MVP

0.15

MPC

0.037

ClinPred

0.086

GERP RS

-2.3

Varity_R

0.18

gMVP

0.24

Mutation Taster

=74/26

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over