rs908581728

Variant names:

• chr7-135571133-C-G
• rs908581728
• NM_015135.3:c.57C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-135571133-C-G
• chr7-135571133-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015135.3(NUP205):​c.57C>G​(p.Asp19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D19D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NUP205 NM_015135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07353631).

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.57C>G	p.Asp19Glu	missense	Exon 2 of 43	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-1029C>G		5_prime_UTR	Exon 2 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.57C>G	p.Asp19Glu	missense	Exon 2 of 43	ENSP00000285968.6	Q92621
	NUP205	ENST00000921555.1		c.153C>G	p.Asp51Glu	missense	Exon 3 of 44	ENSP00000591614.1
	NUP205	ENST00000921547.1		c.57C>G	p.Asp19Glu	missense	Exon 2 of 44	ENSP00000591606.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399832 Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1 AN XY: 696654

African (AFR) AF: 0.00 AC: 0 AN: 29732

American (AMR) AF: 0.00 AC: 0 AN: 38134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24620

East Asian (EAS) AF: 0.00 AC: 0 AN: 34150

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080584

Other (OTH) AF: 0.00 AC: 0 AN: 57194

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.61
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.42	N
PhyloP100		2.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.025	B
Vest4		0.089
MutPred		0.43		Gain of catalytic residue at W21 (P = 0.0286)
MVP		0.53
MPC		0.22
ClinPred		0.49	T
GERP RS		3.4
Varity_R		0.078
gMVP		0.19
Mutation Taster		=293/7	polymorphism

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: rs908581728; hg19: chr7-135255881;