7-135558162-C-T

Variant names:

• chr7-135558162-C-T
• rs6961420
• NM_015135.3:c.28+190C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.287
• Publications: 3 publications found

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]

NUP205 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 13

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1258543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	NM_015135.3	MANE Select	c.28+190C>T		intron	N/A	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-1058+190C>T		intron	N/A	NP_001316363.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	ENST00000285968.11	TSL:1 MANE Select	c.28+190C>T		intron	N/A	ENSP00000285968.6	Q92621
	NUP205	ENST00000921555.1		c.28+190C>T		intron	N/A	ENSP00000591614.1
	NUP205	ENST00000921547.1		c.28+190C>T		intron	N/A	ENSP00000591606.1

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

African (AFR) AF: 0.415 AC: 5451 AN: 13148

American (AMR) AF: 0.415 AC: 9974 AN: 24030

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 10140 AN: 14688

East Asian (EAS) AF: 0.453 AC: 13718 AN: 30308

South Asian (SAS) AF: 0.676 AC: 34473 AN: 50984

European-Finnish (FIN) AF: 0.666 AC: 22611 AN: 33926

Middle Eastern (MID) AF: 0.738 AC: 2027 AN: 2748

European-Non Finnish (NFE) AF: 0.614 AC: 168823 AN: 274794

Other (OTH) AF: 0.591 AC: 15533 AN: 26292

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

African (AFR) AF: 0.413 AC: 17079 AN: 41398

American (AMR) AF: 0.479 AC: 7309 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2280 AN: 5150

South Asian (SAS) AF: 0.669 AC: 3219 AN: 4812

European-Finnish (FIN) AF: 0.661 AC: 6965 AN: 10534

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41569 AN: 67930

Other (OTH) AF: 0.555 AC: 1168 AN: 2106

Alfa AF: 0.525 Hom.: 11043

Bravo AF: 0.521

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Benign	0.75
PhyloP100		0.29
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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