7-135557955-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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 criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.828

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 -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]. Clinvar id is 1619681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.11C>T	p.Pro4Leu	missense_variant	1/43	ENST00000285968.11
NUP205	NM_001329434.2	c.-1075C>T		5_prime_UTR_variant	1/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.11C>T	p.Pro4Leu	missense_variant	1/43	1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.24C>T		non_coding_transcript_exon_variant	1/3	4

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

GnomAD3 exomes AF: 0.00567 AC: 1427 AN: 251458 Hom.: 15 AF XY: 0.00595 AC XY: 809 AN XY: 135902

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 SAS exome AF: 0.00764

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

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00329

Gnomad4 ASJ exome AF: 0.00486

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00788

Gnomad4 FIN exome AF: 0.00562

Gnomad4 NFE exome AF: 0.00689

Gnomad4 OTH exome AF: 0.00546

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

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.00742

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00684 Hom.: 10

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

NUP205-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.87	D;D
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
Varity_R		0.054
gMVP		0.13

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