7-135557955-C-T

Variant names:

• chr7-135557955-C-T
• rs73158973
• NM_015135.3:c.11C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015135.3(NUP205):​c.11C>T​(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,613,878 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (39 hom.)
• Consequence: NUP205 NM_015135.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.828
• Publications: 11 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038821697).
• BP6: Variant 7-135557955-C-T is Benign according to our data. Variant chr7-135557955-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1619681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR,AD gene

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.11C>T	p.Pro4Leu	missense	Exon 1 of 43	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-1075C>T		5_prime_UTR	Exon 1 of 43	NP_001316363.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	ENST00000285968.11	TSL:1 MANE Select	c.11C>T	p.Pro4Leu	missense	Exon 1 of 43	ENSP00000285968.6	Q92621
	NUP205	ENST00000921555.1		c.11C>T	p.Pro4Leu	missense	Exon 1 of 44	ENSP00000591614.1
	NUP205	ENST00000921547.1		c.11C>T	p.Pro4Leu	missense	Exon 1 of 44	ENSP00000591606.1

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 786 AN: 152212 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00742

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00567 AC: 1427 AN: 251458 AF XY: 0.00595

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00582

Gnomad NFE exome AF: 0.00747

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00638 AC: 9325 AN: 1461548 Hom.: 39 Cov.: 29 AF XY: 0.00646 AC XY: 4697 AN XY: 727102

African (AFR) AF: 0.00111 AC: 37 AN: 33472

American (AMR) AF: 0.00329 AC: 147 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00486 AC: 127 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00788 AC: 680 AN: 86254

European-Finnish (FIN) AF: 0.00562 AC: 300 AN: 53418

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5766

European-Non Finnish (NFE) AF: 0.00689 AC: 7655 AN: 1111696

Other (OTH) AF: 0.00546 AC: 330 AN: 60388

GnomAD4 genome AF: 0.00515 AC: 785 AN: 152330 Hom.: 7 Cov.: 32 AF XY: 0.00554 AC XY: 413 AN XY: 74490

African (AFR) AF: 0.00120 AC: 50 AN: 41588

American (AMR) AF: 0.00549 AC: 84 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4828

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00742 AC: 505 AN: 68030

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00628 Hom.: 13

Bravo AF: 0.00444

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00767 AC: 66

ExAC AF: 0.00552 AC: 670

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00981

EpiControl AF: 0.00830

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	NUP205-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.83
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.023
Sift	Benign	0.24	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.15
MVP		0.082
MPC		0.23
ClinPred		0.041	T
GERP RS		0.57
PromoterAI		-0.21	Neutral
Varity_R		0.054
gMVP		0.13
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs73158973; hg19: chr7-135242703; COSMIC: COSV53662226;