dbSNP rs8044753: NUP93:c.*4917G>A (chr16-56849526-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014669.5(NUP93):c.*4917G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,140 control chromosomes in the GnomAD database, including 26,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 26951 hom., cov: 32)

Exomes 𝑓: 0.61 ( 5 hom. )

Consequence

NUP93
NM_014669.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.443

Publications

13 publications found

Variant links:

Genes affected

NUP93 (HGNC:28958): (nucleoporin 93) 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. This gene encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

NUP93 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 12
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NUP93 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014669.5. 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
	NUP93	NM_014669.5	MANE Select	c.*4917G>A		3_prime_UTR	Exon 22 of 22	NP_055484.3
	NUP93	NM_001242795.2		c.*4917G>A		3_prime_UTR	Exon 20 of 20	NP_001229724.1	Q8N1F7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP93	ENST00000308159.10	TSL:1 MANE Select	c.*4917G>A		3_prime_UTR	Exon 22 of 22	ENSP00000310668.5	Q8N1F7-1
	NUP93	ENST00000542526.5	TSL:2	c.*4917G>A		3_prime_UTR	Exon 20 of 20	ENSP00000440235.1	Q8N1F7-2

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89229

AN:

151984

Hom.:

26923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.589

GnomAD4 exome

AF:

0.611

AC:

AN:

Hom.:

Cov.:

AF XY:

0.618

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.615

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.587

AC:

89310

AN:

152104

Hom.:

26951

Cov.:

AF XY:

0.588

AC XY:

43713

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.686

AC:

28458

AN:

41502

American (AMR)

AF:

0.585

AC:

8943

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1766

AN:

3466

East Asian (EAS)

AF:

0.841

AC:

4352

AN:

5174

South Asian (SAS)

AF:

0.674

AC:

3246

AN:

4818

European-Finnish (FIN)

AF:

0.437

AC:

4618

AN:

10566

Middle Eastern (MID)

AF:

0.647

AC:

189

AN:

292

European-Non Finnish (NFE)

AF:

0.531

AC:

36101

AN:

67982

Other (OTH)

AF:

0.592

AC:

1253

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1857

3713

5570

7426

9283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.570

Hom.:

7693

Bravo

AF:

0.604

Asia WGS

AF:

0.741

AC:

2576

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.70

(source)

DANN

Benign

0.22

PhyloP100

-0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over