chr7-135608380-A-G

Variant names:

• chr7-135608380-A-G
• rs4294134
• NM_015135.3:c.3195+1009A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015135.3(NUP205):​c.3195+1009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,136 control chromosomes in the GnomAD database, including 44,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44686 hom., cov: 31)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 33 publications found

Genes affected

NUP205 (HGNC:18658): (nucleoporin 205) This gene encodes a nucleoporin, which is a subunit of the nuclear pore complex that functions in active transport of proteins, RNAs and ribonucleoprotein particles between the nucleus and cytoplasm. Mutations in this gene are associated with steroid-resistant nephrotic syndrome. [provided by RefSeq, Jul 2016]

NUP205 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 13

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	NM_015135.3	MANE Select	c.3195+1009A>G		intron	N/A	NP_055950.2
	NUP205	NM_001329434.2		c.2121+1009A>G		intron	N/A	NP_001316363.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	ENST00000285968.11	TSL:1 MANE Select	c.3195+1009A>G		intron	N/A	ENSP00000285968.6
	NUP205	ENST00000472132.5	TSL:4	c.366+1009A>G		intron	N/A	ENSP00000475665.1
	NUP205	ENST00000463247.1	TSL:4	n.168+1009A>G		intron	N/A	ENSP00000475539.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115533 AN: 152018 Hom.: 44680 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.760 AC: 115573 AN: 152136 Hom.: 44686 Cov.: 31 AF XY: 0.759 AC XY: 56441 AN XY: 74386

African (AFR) AF: 0.652 AC: 27050 AN: 41478

American (AMR) AF: 0.681 AC: 10419 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2915 AN: 3472

East Asian (EAS) AF: 0.532 AC: 2744 AN: 5162

South Asian (SAS) AF: 0.834 AC: 4026 AN: 4828

European-Finnish (FIN) AF: 0.823 AC: 8705 AN: 10580

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57038 AN: 68004

Other (OTH) AF: 0.772 AC: 1634 AN: 2116

Alfa AF: 0.810 Hom.: 217632

Bravo AF: 0.739

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.56
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: rs4294134; hg19: chr7-135293128;