rs730882216

Positions:

chr12-68690746-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PP5_Very_Strong

The NM_020401.4(NUP107):c.303G>A(p.Met101Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000821 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

NUP107
NM_020401.4 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:5

Conservation

PhyloP100: 6.32

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-68690746-G-A is Pathogenic according to our data. Variant chr12-68690746-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-68690746-G-A is described in Lovd as [Likely_pathogenic]. Variant chr12-68690746-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP107	NM_020401.4 link	c.303G>A	p.Met101Ile	missense_variant, splice_region_variant	4/28	ENST00000229179.9	NP_065134.1	P57740-1
NUP107	NM_001330192.2 link	c.216G>A	p.Met72Ile	missense_variant, splice_region_variant	4/28		NP_001317121.1	P57740-2
NUP107	XM_005269037.5 link	c.303G>A	p.Met101Ile	missense_variant, splice_region_variant	4/27		XP_005269094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP107	ENST00000229179.9 link	c.303G>A	p.Met101Ile	missense_variant, splice_region_variant	4/28	1	NM_020401.4	ENSP00000229179.4		P57740-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250664

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2019	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2024	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; RNA studies demonstrate a damaging effect that leads to decreased protein expression (PMID: 28280135); This variant is associated with the following publications: (PMID: 38136965, 28117080, 28280135, 25558065, 30179222) -

Galloway-Mowat syndrome 7

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 13, 2015	- -
Pathogenic, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	Jul 09, 2019	This variant is interpreted as a Pathogenic for Galloway-Mowat syndrome 7. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (PMID:30179222). PP1-Strong => PP1 upgraded in strength to Strong (PMID:28280135; 30179222; 25558065). PM3 =>Multiple unrelated affected individuals homozygous for the variant (PMID:28280135; 30179222; 25558065; 28117080) -

Global developmental delay;C3554634:Light complexion;CN228292:Early onset focal segmental glomerulosclerosis

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

0.064

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.52

T;T;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.068

Sift

Uncertain

0.025

D;D;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.54

MutPred

0.30

Gain of sheet (P = 0.039);.;.;

MVP

0.36

MPC

0.28

ClinPred

0.46

GERP RS

5.6

RBP_binding_hub_radar

0.77

RBP_regulation_power_radar

2.5

Varity_R

0.41

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

1.0

SpliceAI score (max)

0.59

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.59

Position offset: 0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over