6-17632830-C-T

Variant names:

• chr6-17632830-C-T
• rs2274136
• NM_005124.4:c.2479G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005124.4(NUP153):​c.2479G>A​(p.Ala827Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,543,588 control chromosomes in the GnomAD database, including 479,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (43738 hom., cov: 22)
  • Exomes 𝑓: 0.79 (435270 hom.)
• Consequence: NUP153 NM_005124.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 38 publications found

Genes affected

NUP153 (HGNC:8062): (nucleoporin 153) Nuclear pore complexes regulate the transport of macromolecules between the nucleus and cytoplasm. They are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. Nucleoporins are glycoproteins found in nuclear pores and contain characteristic pentapeptide XFXFG repeats as well as O-linked N-acetylglucosamine residues oriented towards the cytoplasm. The protein encoded by this gene has three distinct domains: a N-terminal region containing a pore targeting and an RNA-binding domain domain, a central region containing multiple zinc finger motifs, and a C-terminal region containing multiple XFXFG repeats. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2234004E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005124.4. 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
	NUP153	NM_005124.4	MANE Select	c.2479G>A	p.Ala827Thr	missense	Exon 17 of 22	NP_005115.2
	NUP153	NM_001278209.2		c.2572G>A	p.Ala858Thr	missense	Exon 18 of 23	NP_001265138.1	P49790-3
	NUP153	NM_001278210.2		c.2353G>A	p.Ala785Thr	missense	Exon 16 of 21	NP_001265139.1	P49790-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP153	ENST00000262077.3	TSL:1 MANE Select	c.2479G>A	p.Ala827Thr	missense	Exon 17 of 22	ENSP00000262077.3	P49790-1
	NUP153	ENST00000613258.4	TSL:1	c.2353G>A	p.Ala785Thr	missense	Exon 16 of 21	ENSP00000478627.1	P49790-2
	NUP153	ENST00000537253.5	TSL:2	c.2572G>A	p.Ala858Thr	missense	Exon 18 of 23	ENSP00000444029.1	P49790-3

Frequencies

GnomAD3 genomes AF: 0.774 AC: 112814 AN: 145746 Hom.: 43706 Cov.: 22

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.785

GnomAD2 exomes AF: 0.795 AC: 168682 AN: 212070 AF XY: 0.798

Gnomad AFR exome AF: 0.729

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.805

Gnomad EAS exome AF: 0.884

Gnomad FIN exome AF: 0.778

Gnomad NFE exome AF: 0.781

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.790 AC: 1104346 AN: 1397768 Hom.: 435270 Cov.: 26 AF XY: 0.792 AC XY: 551773 AN XY: 696262

African (AFR) AF: 0.736 AC: 22437 AN: 30488

American (AMR) AF: 0.783 AC: 26557 AN: 33898

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 19327 AN: 23690

East Asian (EAS) AF: 0.908 AC: 35464 AN: 39056

South Asian (SAS) AF: 0.861 AC: 68415 AN: 79446

European-Finnish (FIN) AF: 0.783 AC: 36543 AN: 46668

Middle Eastern (MID) AF: 0.847 AC: 4295 AN: 5070

European-Non Finnish (NFE) AF: 0.781 AC: 845311 AN: 1081896

Other (OTH) AF: 0.799 AC: 45997 AN: 57556

GnomAD4 genome AF: 0.774 AC: 112876 AN: 145820 Hom.: 43738 Cov.: 22 AF XY: 0.776 AC XY: 54760 AN XY: 70538

African (AFR) AF: 0.730 AC: 28657 AN: 39264

American (AMR) AF: 0.787 AC: 11552 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2778 AN: 3458

East Asian (EAS) AF: 0.888 AC: 4418 AN: 4976

South Asian (SAS) AF: 0.858 AC: 3951 AN: 4604

European-Finnish (FIN) AF: 0.783 AC: 6758 AN: 8630

Middle Eastern (MID) AF: 0.867 AC: 241 AN: 278

European-Non Finnish (NFE) AF: 0.778 AC: 52164 AN: 67036

Other (OTH) AF: 0.786 AC: 1568 AN: 1996

Alfa AF: 0.780 Hom.: 133101

Bravo AF: 0.770

TwinsUK AF: 0.768 AC: 2849

ALSPAC AF: 0.768 AC: 2958

ESP6500AA AF: 0.727 AC: 3202

ESP6500EA AF: 0.771 AC: 6634

ExAC AF: 0.791 AC: 96018

Asia WGS AF: 0.872 AC: 3028 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.042	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.83	L
PhyloP100		0.29
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.031
Sift	Benign	0.72	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.049
MPC		0.032
ClinPred		0.0089	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.22
Mutation Taster		=83/17	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2274136; hg19: chr6-17633061; COSMIC: COSV50468526;