NM_018230.3:c.80C>T

Variant names:

• chr1-229508170-G-A
• rs745951330
• NM_018230.3:c.80C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018230.3(NUP133):​c.80C>T​(p.Ser27Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,591,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S27C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: NUP133 NM_018230.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44
• Publications: 0 publications found

Genes affected

NUP133 (HGNC:18016): (nucleoporin 133) The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. The nucleoporin protein encoded by this gene displays evolutionarily conserved interactions with other nucleoporins. This protein, which localizes to both sides of the nuclear pore complex at interphase, remains associated with the complex during mitosis and is targeted at early stages to the reforming nuclear envelope. This protein also localizes to kinetochores of mitotic cells. [provided by RefSeq, Jul 2008]

NUP133-DT (HGNC:55870): (NUP133 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3872633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018230.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP133	NM_018230.3	MANE Select	c.80C>T	p.Ser27Phe	missense	Exon 1 of 26	NP_060700.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP133	ENST00000261396.6	TSL:1 MANE Select	c.80C>T	p.Ser27Phe	missense	Exon 1 of 26	ENSP00000261396.3	Q8WUM0
	NUP133	ENST00000916039.1		c.80C>T	p.Ser27Phe	missense	Exon 1 of 27	ENSP00000586098.1
	NUP133	ENST00000942131.1		c.80C>T	p.Ser27Phe	missense	Exon 1 of 26	ENSP00000612190.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000235 AC: 5 AN: 212750 AF XY: 0.0000169

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 20 AN: 1439628 Hom.: 0 Cov.: 31 AF XY: 0.00000979 AC XY: 7 AN XY: 715252

African (AFR) AF: 0.00 AC: 0 AN: 32214

American (AMR) AF: 0.00 AC: 0 AN: 41948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.00 AC: 0 AN: 37736

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4762

European-Non Finnish (NFE) AF: 0.0000154 AC: 17 AN: 1102796

Other (OTH) AF: 0.0000337 AC: 2 AN: 59304

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000364 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000417 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.044
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.017	D
Polyphen		0.64	P
Vest4		0.49
MVP		0.53
MPC		0.66
ClinPred		0.88	D
GERP RS		5.5
PromoterAI		0.0098	Neutral
Varity_R		0.22
gMVP		0.38
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs745951330; hg19: chr1-229643917;