7-135557999-T-C

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+27T>C 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 1,601,062 control chromosomes in the GnomAD database, including 400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (28 hom., cov: 32)
  • Exomes 𝑓: 0.020 (372 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.184

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=-0.89).
• BP6: Variant 7-135557999-T-C is Benign according to our data. Variant chr7-135557999-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0158 (2409/152268) while in subpopulation NFE AF= 0.0235 (1596/68012). AF 95% confidence interval is 0.0225. There are 28 homozygotes in gnomad4. There are 1111 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.28+27T>C		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-1058+27T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.28+27T>C		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.68T>C		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2409 AN: 152150 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0172 AC: 4330 AN: 251424 Hom.: 51 AF XY: 0.0170 AC XY: 2313 AN XY: 135880

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.00740

Gnomad ASJ exome AF: 0.0400

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00346

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0200

GnomAD4 exome AF: 0.0205 AC: 29655 AN: 1448794 Hom.: 372 Cov.: 27 AF XY: 0.0198 AC XY: 14308 AN XY: 721656

Gnomad4 AFR exome AF: 0.00320

Gnomad4 AMR exome AF: 0.00794

Gnomad4 ASJ exome AF: 0.0404

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.0269

Gnomad4 NFE exome AF: 0.0229

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0158 AC: 2409 AN: 152268 Hom.: 28 Cov.: 32 AF XY: 0.0149 AC XY: 1111 AN XY: 74450

Gnomad4 AFR AF: 0.00378

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0126 Hom.: 4

Bravo AF: 0.0148

Asia WGS AF: 0.000866 AC: 3 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

Dec 29, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.5
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs117892953; hg19: chr7-135242747; COSMIC: COSV53660832;