7-135571078-G-A

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.29-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,522,034 control chromosomes in the GnomAD database, including 474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (79 hom., cov: 28)
  • Exomes 𝑓: 0.017 (395 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.357

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=-0.86).
• BP6: Variant 7-135571078-G-A is Benign according to our data. Variant chr7-135571078-G-A is described in ClinVar as [Benign]. Clinvar id is 1262162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.29-27G>A		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-1057-27G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.29-27G>A		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.284-27G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3707 AN: 148110 Hom.: 79 Cov.: 28

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.00682

Gnomad SAS AF: 0.0772

Gnomad FIN AF: 0.00150

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0203

GnomAD3 exomes AF: 0.0189 AC: 3934 AN: 207784 Hom.: 114 AF XY: 0.0209 AC XY: 2387 AN XY: 114404

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.00765

Gnomad ASJ exome AF: 0.0230

Gnomad EAS exome AF: 0.00737

Gnomad SAS exome AF: 0.0671

Gnomad FIN exome AF: 0.00266

Gnomad NFE exome AF: 0.00943

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0169 AC: 23210 AN: 1373836 Hom.: 395 Cov.: 28 AF XY: 0.0180 AC XY: 12316 AN XY: 683584

Gnomad4 AFR exome AF: 0.0522

Gnomad4 AMR exome AF: 0.00890

Gnomad4 ASJ exome AF: 0.0249

Gnomad4 EAS exome AF: 0.00820

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.00268

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0251 AC: 3714 AN: 148198 Hom.: 79 Cov.: 28 AF XY: 0.0261 AC XY: 1880 AN XY: 72150

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.00684

Gnomad4 SAS AF: 0.0770

Gnomad4 FIN AF: 0.00150

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0196

Alfa AF: 0.0191 Hom.: 18

Bravo AF: 0.0252

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

Feb 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.1
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs115498909; hg19: chr7-135255826;