7-135571306-G-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.171+59G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,121,498 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (70 hom., cov: 29)
  • Exomes 𝑓: 0.015 (232 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.616

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=-0.98).
• BP6: Variant 7-135571306-G-C is Benign according to our data. Variant chr7-135571306-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316796.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.171+59G>C		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-915+59G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.171+59G>C		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.426+59G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3538 AN: 147762 Hom.: 70 Cov.: 29

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.00668

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.000867

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0202

GnomAD4 exome AF: 0.0151 AC: 14690 AN: 973660 Hom.: 232 AF XY: 0.0154 AC XY: 7377 AN XY: 479650

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.00901

Gnomad4 ASJ exome AF: 0.0247

Gnomad4 EAS exome AF: 0.00800

Gnomad4 SAS exome AF: 0.0617

Gnomad4 FIN exome AF: 0.00261

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.0239 AC: 3540 AN: 147838 Hom.: 70 Cov.: 29 AF XY: 0.0247 AC XY: 1778 AN XY: 71930

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.00669

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.000867

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.0195

Alfa AF: 0.00631 Hom.: 2

Bravo AF: 0.0252

Asia WGS AF: 0.0440 AC: 150 AN: 3444

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.66
Dann	Benign	0.36

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: rs141765692; hg19: chr7-135256054;