Genetic Variant NUP107:c.187+19A>T (chr12-68689638-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_020401.4(NUP107):c.187+19A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000777 in 1,496,636 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

NUP107
NM_020401.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.860

Publications

2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 12-68689638-A-T is Benign according to our data. Variant chr12-68689638-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1629594.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020401.4. 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
	NUP107	NM_020401.4	MANE Select	c.187+19A>T		intron	N/A	NP_065134.1	P57740-1
	NUP107	NM_001330192.2		c.72+19A>T		intron	N/A	NP_001317121.1	P57740-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NUP107	ENST00000229179.9	TSL:1 MANE Select	c.187+19A>T	intron	N/A	ENSP00000229179.4	P57740-1
NUP107	ENST00000535718.5	TSL:1	n.187+19A>T	intron	N/A	ENSP00000445567.1	G3V1T4
NUP107	ENST00000908487.1		c.187+19A>T	intron	N/A	ENSP00000578546.1

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000683

AC:

163

AN:

238754

AF XY:

0.000837

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000517

Gnomad ASJ exome

AF:

0.000637

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000794

AC:

1068

AN:

1344414

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

558

AN XY:

674542

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

30536

American (AMR)

AF:

0.000606

AC:

AN:

41248

Ashkenazi Jewish (ASJ)

AF:

0.000638

AC:

AN:

25090

East Asian (EAS)

AF:

0.00

AC:

AN:

39038

South Asian (SAS)

AF:

0.00

AC:

AN:

81336

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.000976

AC:

988

AN:

1011926

Other (OTH)

AF:

0.000567

AC:

AN:

56452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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:

0.000624

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41462

American (AMR)

AF:

0.000393

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00119

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000933

Hom.:

Bravo

AF:

0.000536

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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