dbSNP rs150565530: NUP210:p.Val1781Met (chr3-13319805-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_024923.4(NUP210):c.5341G>A(p.Val1781Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

NUP210
NM_024923.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP210	NM_024923.4 link	c.5341G>A	p.Val1781Met	missense_variant	Exon 37 of 40	ENST00000254508.7	NP_079199.2	Q8TEM1-1
NUP210	XM_047447795.1 link	c.2725G>A	p.Val909Met	missense_variant	Exon 19 of 22		XP_047303751.1
NUP210	XM_047447797.1 link	c.2692G>A	p.Val898Met	missense_variant	Exon 19 of 22		XP_047303753.1
NUP210	XM_047447796.1 link	c.2656G>A	p.Val886Met	missense_variant	Exon 19 of 22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUP210	ENST00000254508.7 link	c.5341G>A	p.Val1781Met	missense_variant	Exon 37 of 40	2	NM_024923.4	ENSP00000254508.5	Q8TEM1-1
NUP210	ENST00000695489.1 link	n.1069G>A		non_coding_transcript_exon_variant	Exon 1 of 4
NUP210	ENST00000695490.1 link	n.*769G>A		non_coding_transcript_exon_variant	Exon 19 of 22			ENSP00000511960.1	A0A8Q3WKI1
NUP210	ENST00000695490.1 link	n.*769G>A		3_prime_UTR_variant	Exon 19 of 22			ENSP00000511960.1	A0A8Q3WKI1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251374

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727240

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5341G>A (p.V1781M) alteration is located in exon 37 (coding exon 37) of the NUP210 gene. This alteration results from a G to A substitution at nucleotide position 5341, causing the valine (V) at amino acid position 1781 to be replaced by a methionine (M). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

0.11

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.5

REVEL

Benign

0.21

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.65

Vest4

0.69

MVP

0.34

MPC

0.47

ClinPred

0.64

GERP RS

4.8

Varity_R

0.17

gMVP

0.85

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