Variant 3-13319116-G-A 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_024923.4(NUP210):c.5519C>T(p.Pro1840Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NUP210
NM_024923.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

NUP210 (HGNC:30052): (nucleoporin 210) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a membrane-spanning glycoprotein that is a major component of the nuclear pore complex. Multiple pseudogenes related to this gene are located on chromosome 3. [provided by RefSeq, Jul 2013]

NUP210 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=0.142649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUP210	NM_024923.4 linkuse as main transcript	c.5519C>T	p.Pro1840Leu	missense_variant	39/40	ENST00000254508.7	NP_079199.2
NUP210	XM_047447795.1 linkuse as main transcript	c.2903C>T	p.Pro968Leu	missense_variant	21/22		XP_047303751.1
NUP210	XM_047447797.1 linkuse as main transcript	c.2870C>T	p.Pro957Leu	missense_variant	21/22		XP_047303753.1
NUP210	XM_047447796.1 linkuse as main transcript	c.2834C>T	p.Pro945Leu	missense_variant	21/22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP210	ENST00000254508.7 linkuse as main transcript	c.5519C>T	p.Pro1840Leu	missense_variant	39/40	2	NM_024923.4	ENSP00000254508	P1	Q8TEM1-1
NUP210	ENST00000695489.1 linkuse as main transcript	n.1247C>T		non_coding_transcript_exon_variant	3/4
NUP210	ENST00000695490.1 linkuse as main transcript	c.*947C>T		3_prime_UTR_variant, NMD_transcript_variant	21/22			ENSP00000511960

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 12, 2023

The c.5519C>T (p.P1840L) alteration is located in exon 39 (coding exon 39) of the NUP210 gene. This alteration results from a C to T substitution at nucleotide position 5519, causing the proline (P) at amino acid position 1840 to be replaced by a leucine (L). 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

0.090

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.075

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.66

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.025

Sift

Uncertain

0.018

Sift4G

Benign

0.12

Polyphen

0.085

Vest4

0.25

MutPred

0.50

Gain of sheet (P = 0.0061);

MVP

0.35

MPC

0.18

ClinPred

0.20

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over