Variant chr3-13317754-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024923.4(NUP210):c.5591C>T(p.Pro1864Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,459,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000014 ( 0 hom. )

Consequence

NUP210
NM_024923.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.580

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039270937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NUP210	NM_024923.4 linkuse as main transcript	c.5591C>T	p.Pro1864Leu	missense_variant	40/40	ENST00000254508.7
NUP210	XM_047447795.1 linkuse as main transcript	c.2975C>T	p.Pro992Leu	missense_variant	22/22
NUP210	XM_047447797.1 linkuse as main transcript	c.2942C>T	p.Pro981Leu	missense_variant	22/22
NUP210	XM_047447796.1 linkuse as main transcript	c.2906C>T	p.Pro969Leu	missense_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210	ENST00000254508.7 linkuse as main transcript	c.5591C>T	p.Pro1864Leu	missense_variant	40/40	2	NM_024923.4	P1	Q8TEM1-1
NUP210	ENST00000695489.1 linkuse as main transcript	n.1319C>T		non_coding_transcript_exon_variant	4/4
NUP210	ENST00000695490.1 linkuse as main transcript	c.*1019C>T		3_prime_UTR_variant, NMD_transcript_variant	22/22

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000288

AC:

AN:

243318

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

131878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1459206

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

725550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 22, 2023

The c.5591C>T (p.P1864L) alteration is located in exon 40 (coding exon 40) of the NUP210 gene. This alteration results from a C to T substitution at nucleotide position 5591, causing the proline (P) at amino acid position 1864 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

0.066

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.9

DANN

Benign

0.34

DEOGEN2

Benign

0.027

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.59

M_CAP

Benign

0.0070

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.41

REVEL

Benign

0.035

Sift

Benign

0.66

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.017

MutPred

0.20

Loss of glycosylation at P1861 (P = 0.0077);

MVP

0.20

MPC

0.17

ClinPred

0.0088

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.014

gMVP

0.36

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