rs12530845

Positions:

• chr7-135645230-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
NUP205	NM_015135.3	c.5683+212T>C		intron_variant		ENST00000285968.11	NP_055950.2
NUP205	NM_001329434.2	c.4609+212T>C		intron_variant			NP_001316363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP205	ENST00000285968.11	c.5683+212T>C		intron_variant		1	NM_015135.3	ENSP00000285968	P1

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

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.198

Alfa AF: 0.203 Hom.: 1471

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.9
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs12530845; hg19: chr7-135329978;