7-23185244-A-T

Position:

• chr7-23185244-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007342.3(NUP42):​c.296A>T​(p.Glu99Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP42 NM_007342.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

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 (HGNC:):

ACMG classification

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=0.18292764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP42	NM_007342.3	c.296A>T	p.Glu99Val	missense_variant	2/7	ENST00000258742.10	NP_031368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP42	ENST00000258742.10	c.296A>T	p.Glu99Val	missense_variant	2/7	1	NM_007342.3	ENSP00000258742.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.296A>T (p.E99V) alteration is located in exon 2 (coding exon 2) of the NUPL2 gene. This alteration results from a A to T substitution at nucleotide position 296, causing the glutamic acid (E) at amino acid position 99 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	-0.0088
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.087
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.30	B;.;.
Vest4		0.43
MutPred		0.24		Loss of disorder (P = 0.1044);Loss of disorder (P = 0.1044);Loss of disorder (P = 0.1044);
MVP		0.64
MPC		0.082
ClinPred		0.87	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-23224863;