7-135558225-T-G

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.28+253T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 546,024 control chromosomes in the GnomAD database, including 15,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4340 hom., cov: 31)
  • Exomes 𝑓: 0.22 (11642 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460

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=-0.8).
• BP6: Variant 7-135558225-T-G is Benign according to our data. Variant chr7-135558225-T-G is described in ClinVar as [Benign]. Clinvar id is 1289264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.28+253T>G		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-1058+253T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.28+253T>G		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.283+11T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33683 AN: 151814 Hom.: 4326 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.223 AC: 88030 AN: 394092 Hom.: 11642 Cov.: 0 AF XY: 0.217 AC XY: 45368 AN XY: 208846

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.222 AC: 33723 AN: 151932 Hom.: 4340 Cov.: 31 AF XY: 0.224 AC XY: 16612 AN XY: 74264

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.238

Alfa AF: 0.207 Hom.: 557

Bravo AF: 0.240

Asia WGS AF: 0.341 AC: 1185 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	-0.80
Cadd	Benign	7.7
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs11763242; hg19: chr7-135242973;