7-135571298-C-T

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.171+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,174,900 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (94 hom., cov: 29)
  • Exomes 𝑓: 0.019 (458 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0430

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=-0.96).
• BP6: Variant 7-135571298-C-T is Benign according to our data. Variant chr7-135571298-C-T is described in ClinVar as [Benign]. Clinvar id is 1241367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.171+51C>T		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-915+51C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.171+51C>T		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.426+51C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4028 AN: 143676 Hom.: 94 Cov.: 29

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.00121

Gnomad MID AF: 0.0175

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0231

GnomAD3 exomes AF: 0.0219 AC: 2699 AN: 123436 Hom.: 96 AF XY: 0.0227 AC XY: 1551 AN XY: 68188

Gnomad AFR exome AF: 0.0538

Gnomad AMR exome AF: 0.00825

Gnomad ASJ exome AF: 0.0205

Gnomad EAS exome AF: 0.0637

Gnomad SAS exome AF: 0.0975

Gnomad FIN exome AF: 0.00253

Gnomad NFE exome AF: 0.00814

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0189 AC: 19491 AN: 1031160 Hom.: 458 Cov.: 15 AF XY: 0.0194 AC XY: 9846 AN XY: 506494

Gnomad4 AFR exome AF: 0.0540

Gnomad4 AMR exome AF: 0.00935

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.0738

Gnomad4 SAS exome AF: 0.0950

Gnomad4 FIN exome AF: 0.00263

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0280 AC: 4027 AN: 143740 Hom.: 94 Cov.: 29 AF XY: 0.0297 AC XY: 2065 AN XY: 69508

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.0590

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.00121

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0224

Alfa AF: 0.0207 Hom.: 9

Bravo AF: 0.0280

Asia WGS AF: 0.0810 AC: 275 AN: 3420

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	-0.96
Cadd	Benign	2.1
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: rs76038385; hg19: chr7-135256046;