rs864321632

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PP3_StrongPP5_Moderate

The NM_020401.4(NUP107):c.2492A>C(p.Asp831Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NUP107
NM_020401.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 8.26

Publications

4 publications found

Variant links:

Genes affected

NUP107 (HGNC:29914): (nucleoporin 107) This gene encodes a member of the nucleoporin family. The protein is localized to the nuclear rim and is an essential component of the nuclear pore complex (NPC). All molecules entering or leaving the nucleus either diffuse through or are actively transported by the NPC. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

NUP107 Gene-Disease associations (from GenCC):

Galloway-Mowat syndrome 7
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
nephrotic syndrome, type 11
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
ovarian dysgenesis 6
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
46 XX gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Galloway-Mowat syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NUP107 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

PP5

Variant 12-68735334-A-C is Pathogenic according to our data. Variant chr12-68735334-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 219127.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP107	NM_020401.4 link	c.2492A>C	p.Asp831Ala	missense_variant	Exon 26 of 28	ENST00000229179.9	NP_065134.1	P57740-1
NUP107	NM_001330192.2 link	c.2405A>C	p.Asp802Ala	missense_variant	Exon 26 of 28		NP_001317121.1	P57740-2
NUP107	XM_005269037.5 link	c.2432A>C	p.Asp811Ala	missense_variant	Exon 25 of 27		XP_005269094.1
NUP107	XM_047429177.1 link	c.1556A>C	p.Asp519Ala	missense_variant	Exon 16 of 18		XP_047285133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP107	ENST00000229179.9 link	c.2492A>C	p.Asp831Ala	missense_variant	Exon 26 of 28	1	NM_020401.4	ENSP00000229179.4		P57740-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251334

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460560

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.000202

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110904

Other (OTH)

AF:

0.0000166

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 11

Pathogenic:2

Jan 03, 2022

3billion

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Same nucleotide change resulting in same amino acid change has been previously reported to be associated with NUP107 related disorder (ClinVar ID: VCV000219127, PMID:26411495, PS1_P). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals (PMID: 26411495, PM3_S) and it was co-segregated with Nephrotic syndrome, type 11 in multiple affected family members (PMID: 26411495, PP1_P). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (, PS3_S). A missense variant is a common mechanism associated with Nephrotic syndrome (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. -

Oct 01, 2015

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

3.0

M;.;.

PhyloP100

8.3

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-6.8

D;D;D

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.93

MutPred

0.86

Loss of solvent accessibility (P = 0.0509);.;.;

MVP

0.75

MPC

1.0

ClinPred

0.91

GERP RS

4.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.88

gMVP

0.77

Mutation Taster

=8/92

disease causing (ClinVar)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over