7-135558264-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015135.3(NUP205):c.28+292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 448,580 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (14 hom., cov: 32)
  • Exomes 𝑓: 0.013 (35 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291

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=-0.87).
• BP6: Variant 7-135558264-A-G is Benign according to our data. Variant chr7-135558264-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.01 (1521/152122) while in subpopulation SAS AF= 0.0253 (122/4816). AF 95% confidence interval is 0.0217. There are 14 homozygotes in gnomad4. There are 784 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.28+292A>G		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-1058+292A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.28+292A>G		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.283+50A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1520 AN: 152004 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00230

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00953

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0128 AC: 3794 AN: 296458 Hom.: 35 Cov.: 0 AF XY: 0.0137 AC XY: 2139 AN XY: 156022

Gnomad4 AFR exome AF: 0.00184

Gnomad4 AMR exome AF: 0.00668

Gnomad4 ASJ exome AF: 0.00951

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0133

GnomAD4 genome AF: 0.0100 AC: 1521 AN: 152122 Hom.: 14 Cov.: 32 AF XY: 0.0105 AC XY: 784 AN XY: 74360

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00589

Gnomad4 ASJ AF: 0.00953

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0128 Hom.: 2

Bravo AF: 0.00775

Asia WGS AF: 0.00837 AC: 30 AN: 3478

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

Apr 20, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.0
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73158974; hg19: chr7-135243012;