rs12530845

Variant names:

• chr7-135645230-T-C
• rs12530845
• NM_015135.3:c.5683+212T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015135.3(NUP205):​c.5683+212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,150 control chromosomes in the GnomAD database, including 3,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3521 hom., cov: 32)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0870
• Publications: 11 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-135645230-T-C is Benign according to our data. Variant chr7-135645230-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP205	NM_015135.3	c.5683+212T>C		intron_variant	Intron 40 of 42	ENST00000285968.11	NP_055950.2
NUP205	NM_001329434.2	c.4609+212T>C		intron_variant	Intron 40 of 42		NP_001316363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP205	ENST00000285968.11	c.5683+212T>C		intron_variant	Intron 40 of 42	1	NM_015135.3	ENSP00000285968.6

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32178 AN: 152032 Hom.: 3524 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.212 AC: 32186 AN: 152150 Hom.: 3521 Cov.: 32 AF XY: 0.214 AC XY: 15902 AN XY: 74398

African (AFR) AF: 0.233 AC: 9683 AN: 41510

American (AMR) AF: 0.213 AC: 3254 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5170

South Asian (SAS) AF: 0.313 AC: 1511 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1950 AN: 10592

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13087 AN: 67992

Other (OTH) AF: 0.198 AC: 419 AN: 2112

Alfa AF: 0.205 Hom.: 6576

Bravo AF: 0.212

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		-0.087
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12530845; hg19: chr7-135329978;