Variant 3-13319251-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024923.4(NUP210):c.5458G>C(p.Gly1820Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NUP210
NM_024923.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP210	NM_024923.4 link	c.5458G>C	p.Gly1820Arg	missense_variant	38/40	ENST00000254508.7	NP_079199.2	Q8TEM1-1
NUP210	XM_047447795.1 link	c.2842G>C	p.Gly948Arg	missense_variant	20/22		XP_047303751.1
NUP210	XM_047447797.1 link	c.2809G>C	p.Gly937Arg	missense_variant	20/22		XP_047303753.1
NUP210	XM_047447796.1 link	c.2773G>C	p.Gly925Arg	missense_variant	20/22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUP210	ENST00000254508.7 link	c.5458G>C	p.Gly1820Arg	missense_variant	38/40	2	NM_024923.4	ENSP00000254508.5	Q8TEM1-1
NUP210	ENST00000695489.1 link	n.1186G>C		non_coding_transcript_exon_variant	2/4
NUP210	ENST00000695490.1 link	n.*886G>C		non_coding_transcript_exon_variant	20/22			ENSP00000511960.1	A0A8Q3WKI1
NUP210	ENST00000695490.1 link	n.*886G>C		3_prime_UTR_variant	20/22			ENSP00000511960.1	A0A8Q3WKI1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249592

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461006

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000897

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000247

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

Nov 24, 2024

The c.5458G>C (p.G1820R) alteration is located in exon 38 (coding exon 38) of the NUP210 gene. This alteration results from a G to C substitution at nucleotide position 5458, causing the glycine (G) at amino acid position 1820 to be replaced by an arginine (R). 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.25

Sift

Uncertain

0.027

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.86

MutPred

0.72

Gain of methylation at G1820 (P = 0.031);

MVP

0.69

MPC

0.56

ClinPred

0.91

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.93

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