Variant chr3-13319244-G-A 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.5465C>T(p.Ala1822Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,460,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NUP210
NM_024923.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.89

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, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUP210	NM_024923.4 linkuse as main transcript	c.5465C>T	p.Ala1822Val	missense_variant	38/40	ENST00000254508.7	NP_079199.2
NUP210	XM_047447795.1 linkuse as main transcript	c.2849C>T	p.Ala950Val	missense_variant	20/22		XP_047303751.1
NUP210	XM_047447797.1 linkuse as main transcript	c.2816C>T	p.Ala939Val	missense_variant	20/22		XP_047303753.1
NUP210	XM_047447796.1 linkuse as main transcript	c.2780C>T	p.Ala927Val	missense_variant	20/22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP210	ENST00000254508.7 linkuse as main transcript	c.5465C>T	p.Ala1822Val	missense_variant	38/40	2	NM_024923.4	ENSP00000254508	P1	Q8TEM1-1
NUP210	ENST00000695489.1 linkuse as main transcript	n.1193C>T		non_coding_transcript_exon_variant	2/4
NUP210	ENST00000695490.1 linkuse as main transcript	c.*893C>T		3_prime_UTR_variant, NMD_transcript_variant	20/22			ENSP00000511960

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248862

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134554

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:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460696

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Oct 05, 2021

The c.5465C>T (p.A1822V) alteration is located in exon 38 (coding exon 38) of the NUP210 gene. This alteration results from a C to T substitution at nucleotide position 5465, causing the alanine (A) at amino acid position 1822 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

0.31

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.90

MutPred

0.46

Loss of helix (P = 0.028);

MVP

0.68

MPC

0.56

ClinPred

0.86

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.86

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

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