NM_020401.4:c.9-91delT

Variant names:

• chr12-68688870-CT-C
• rs35079356
• NM_020401.4:c.9-91delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020401.4(NUP107):​c.9-91delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 886,082 control chromosomes in the GnomAD database, including 427 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (91 hom., cov: 32)
  • Exomes 𝑓: 0.027 (336 hom.)
• Consequence: NUP107 NM_020401.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.546
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-68688870-CT-C is Benign according to our data. Variant chr12-68688870-CT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1201224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0303 (4613/152256) while in subpopulation AFR AF = 0.0462 (1919/41546). AF 95% confidence interval is 0.0445. There are 91 homozygotes in GnomAd4. There are 2294 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 91 AR,AD gene

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.9-91delT		intron	N/A	NP_065134.1	P57740-1
	NUP107	NM_001330192.2		c.-107-91delT		intron	N/A	NP_001317121.1	P57740-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP107	ENST00000229179.9	TSL:1 MANE Select	c.9-91delT		intron	N/A	ENSP00000229179.4	P57740-1
	NUP107	ENST00000535718.5	TSL:1	n.9-91delT		intron	N/A	ENSP00000445567.1	G3V1T4
	NUP107	ENST00000908487.1		c.9-91delT		intron	N/A	ENSP00000578546.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4614 AN: 152138 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0264

GnomAD4 exome AF: 0.0266 AC: 19484 AN: 733826 Hom.: 336 AF XY: 0.0271 AC XY: 10332 AN XY: 381306

African (AFR) AF: 0.0475 AC: 868 AN: 18278

American (AMR) AF: 0.0319 AC: 830 AN: 25982

Ashkenazi Jewish (ASJ) AF: 0.00424 AC: 73 AN: 17202

East Asian (EAS) AF: 0.000183 AC: 6 AN: 32736

South Asian (SAS) AF: 0.0461 AC: 2533 AN: 54970

European-Finnish (FIN) AF: 0.0403 AC: 1876 AN: 46600

Middle Eastern (MID) AF: 0.0167 AC: 63 AN: 3776

European-Non Finnish (NFE) AF: 0.0250 AC: 12475 AN: 499628

Other (OTH) AF: 0.0219 AC: 760 AN: 34654

GnomAD4 genome AF: 0.0303 AC: 4613 AN: 152256 Hom.: 91 Cov.: 32 AF XY: 0.0308 AC XY: 2294 AN XY: 74438

African (AFR) AF: 0.0462 AC: 1919 AN: 41546

American (AMR) AF: 0.0297 AC: 454 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4826

European-Finnish (FIN) AF: 0.0377 AC: 400 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1572 AN: 68028

Other (OTH) AF: 0.0261 AC: 55 AN: 2108

Alfa AF: 0.0114 Hom.: 2

Bravo AF: 0.0285

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35079356; hg19: chr12-69082650;