chr16-56758527-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014669.5(NUP93):c.180-11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,596,650 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 21 hom. )

Consequence

NUP93
NM_014669.5 intron

Scores

Splicing: ADA: 0.9148

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.132

Publications

1 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: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-56758527-T-A is Benign according to our data. Variant chr16-56758527-T-A is described in ClinVar as Benign. ClinVar VariationId is 1640265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00167 (255/152266) while in subpopulation EAS AF = 0.0424 (220/5184). AF 95% confidence interval is 0.0378. There are 7 homozygotes in GnomAd4. There are 149 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP93	NM_014669.5 link	c.180-11T>A		intron_variant	Intron 2 of 21	ENST00000308159.10	NP_055484.3	Q8N1F7-1
NUP93	XM_005256263.4 link	c.180-11T>A		intron_variant	Intron 2 of 21		XP_005256320.1	Q8N1F7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP93	ENST00000308159.10 link	c.180-11T>A		intron_variant	Intron 2 of 21	1	NM_014669.5	ENSP00000310668.5		Q8N1F7-1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0423

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00345

AC:

866

AN:

251278

AF XY:

0.00326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.0444

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00101

AC:

1456

AN:

1444384

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

696

AN XY:

719770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33094

American (AMR)

AF:

0.000112

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.000461

AC:

AN:

26020

East Asian (EAS)

AF:

0.0300

AC:

1189

AN:

39604

South Asian (SAS)

AF:

0.000512

AC:

AN:

85884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000301

AC:

AN:

1096158

Other (OTH)

AF:

0.00289

AC:

173

AN:

59816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

150

226

301

376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00167

AC:

255

AN:

152266

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41554

American (AMR)

AF:

0.00124

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.0424

AC:

220

AN:

5184

South Asian (SAS)

AF:

0.000416

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68012

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.00193

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 12

Benign:1

Feb 10, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.91

dbscSNV1_RF

Benign

0.53

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over