1-229508230-G-A

Variant names:

• chr1-229508230-G-A
• rs745909095
• NM_018230.3:c.20C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018230.3(NUP133):​c.20C>T​(p.Ser7Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000312 in 1,540,012 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NUP133 NM_018230.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10191816).

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.20C>T	p.Ser7Phe	missense	Exon 1 of 26	NP_060700.2
	NUP133-DT	NR_110630.1		n.-200G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP133	ENST00000261396.6	TSL:1 MANE Select	c.20C>T	p.Ser7Phe	missense	Exon 1 of 26	ENSP00000261396.3	Q8WUM0
	NUP133	ENST00000916039.1		c.20C>T	p.Ser7Phe	missense	Exon 1 of 27	ENSP00000586098.1
	NUP133	ENST00000942131.1		c.20C>T	p.Ser7Phe	missense	Exon 1 of 26	ENSP00000612190.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

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: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000402 AC: 6 AN: 149214 AF XY: 0.0000359

Gnomad AFR exome AF: 0.000803

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000180 AC: 25 AN: 1387646 Hom.: 0 Cov.: 31 AF XY: 0.0000160 AC XY: 11 AN XY: 686260

African (AFR) AF: 0.000766 AC: 23 AN: 30020

American (AMR) AF: 0.00 AC: 0 AN: 30512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23818

East Asian (EAS) AF: 0.00 AC: 0 AN: 35386

South Asian (SAS) AF: 0.00 AC: 0 AN: 78684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077618

Other (OTH) AF: 0.0000349 AC: 2 AN: 57246

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152366 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74514

African (AFR) AF: 0.000553 AC: 23 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.0000679 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.42
MVP		0.61
MPC		0.66
ClinPred		0.28	T
GERP RS		5.5
PromoterAI		-0.022	Neutral
Varity_R		0.50
gMVP		0.40
Mutation Taster		=55/45	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: rs745909095; hg19: chr1-229643977;