rs864321687

chr12-68715733-CAGAAG-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020401.4(NUP107):c.1079_1083del(p.Glu360GlyfsTer6) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,577,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: NUP107 NM_020401.4 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.09

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-68715733-CAGAAG-C is Pathogenic according to our data. Variant chr12-68715733-CAGAAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 219128.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP107	NM_020401.4	c.1079_1083del	p.Glu360GlyfsTer6	frameshift_variant, splice_region_variant	12/28	ENST00000229179.9
NUP107	NM_001330192.2	c.992_996del	p.Glu331GlyfsTer6	frameshift_variant, splice_region_variant	12/28
NUP107	XM_005269037.5	c.1079_1083del	p.Glu360GlyfsTer6	frameshift_variant, splice_region_variant	12/27
NUP107	XM_047429177.1	c.143_147del	p.Glu48GlyfsTer6	frameshift_variant, splice_region_variant	2/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP107	ENST00000229179.9	c.1079_1083del	p.Glu360GlyfsTer6	frameshift_variant, splice_region_variant	12/28	1	NM_020401.4	P1
NUP107	ENST00000535718.5	c.*622_*626del		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	11/25	1
NUP107	ENST00000378905.6	c.626_630del	p.Glu209GlyfsTer6	frameshift_variant, splice_region_variant	12/26	5
NUP107	ENST00000539906.5	c.992_996del	p.Glu331GlyfsTer6	frameshift_variant, splice_region_variant	12/28	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250606 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000105 AC: 15 AN: 1425100 Hom.: 0 AF XY: 0.0000141 AC XY: 10 AN XY: 711578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000380

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephrotic syndrome, type 11 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs864321687; hg19: chr12-69109513;