dbSNP rs145799181: NUP210:p.Arg1835Leu (chr3-13319131-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024923.4(NUP210):c.5504G>T(p.Arg1835Leu) 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 1,457,470 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1835Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NUP210
NM_024923.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38960165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP210	NM_024923.4 link	c.5504G>T	p.Arg1835Leu	missense_variant	Exon 39 of 40	ENST00000254508.7	NP_079199.2	Q8TEM1-1
NUP210	XM_047447795.1 link	c.2888G>T	p.Arg963Leu	missense_variant	Exon 21 of 22		XP_047303751.1
NUP210	XM_047447797.1 link	c.2855G>T	p.Arg952Leu	missense_variant	Exon 21 of 22		XP_047303753.1
NUP210	XM_047447796.1 link	c.2819G>T	p.Arg940Leu	missense_variant	Exon 21 of 22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUP210	ENST00000254508.7 link	c.5504G>T	p.Arg1835Leu	missense_variant	Exon 39 of 40	2	NM_024923.4	ENSP00000254508.5	Q8TEM1-1
NUP210	ENST00000695489.1 link	n.1232G>T		non_coding_transcript_exon_variant	Exon 3 of 4
NUP210	ENST00000695490.1 link	n.*932G>T		non_coding_transcript_exon_variant	Exon 21 of 22			ENSP00000511960.1	A0A8Q3WKI1
NUP210	ENST00000695490.1 link	n.*932G>T		3_prime_UTR_variant	Exon 21 of 22			ENSP00000511960.1	A0A8Q3WKI1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457470

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724282

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:

0.0000188

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.78

M_CAP

Benign

0.052

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.087

Sift

Benign

0.12

Sift4G

Benign

0.11

Polyphen

0.72

Vest4

0.46

MutPred

0.56

Loss of glycosylation at P1840 (P = 0.0731);

MVP

0.41

MPC

0.47

ClinPred

0.77

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.081

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over