7-135558162-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.28+190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 622,774 control chromosomes in the GnomAD database, including 110,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23472 hom., cov: 31)
  • Exomes 𝑓: 0.60 (86688 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.287

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=-0.76).
• BP6: Variant 7-135558162-C-T is Benign according to our data. Variant chr7-135558162-C-T is described in ClinVar as [Benign]. Clinvar id is 1258543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.28+190C>T		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-1058+190C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.28+190C>T		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.231C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82856 AN: 151736 Hom.: 23476 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.600 AC: 282750 AN: 470918 Hom.: 86688 Cov.: 4 AF XY: 0.608 AC XY: 152888 AN XY: 251286

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.546 AC: 82861 AN: 151856 Hom.: 23472 Cov.: 31 AF XY: 0.551 AC XY: 40875 AN XY: 74214

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.555

Alfa AF: 0.532 Hom.: 2857

Bravo AF: 0.521

Asia WGS AF: 0.513 AC: 1786 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	-0.76
Cadd	Benign	9.1
Dann	Benign	0.75

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: rs6961420; hg19: chr7-135242910; COSMIC: COSV53668187;