rs869312984

Variant names:

• chr7-135648501-T-C
• rs869312984
• NM_015135.3:c.5984T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-135648501-T-C
• chr7-135648501-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3 PP5

The NM_015135.3(NUP205):​c.5984T>C​(p.Phe1995Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000619 in 1,453,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: NUP205 NM_015135.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.96
• Publications: 5 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, 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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813
• PP5: Variant 7-135648501-T-C is Pathogenic according to our data. Variant chr7-135648501-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 224969.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	NM_015135.3	MANE Select	c.5984T>C	p.Phe1995Ser	missense	Exon 43 of 43	NP_055950.2
	NUP205	NM_001329434.2		c.4910T>C	p.Phe1637Ser	missense	Exon 43 of 43	NP_001316363.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	ENST00000285968.11	TSL:1 MANE Select	c.5984T>C	p.Phe1995Ser	missense	Exon 43 of 43	ENSP00000285968.6
	NUP205	ENST00000921555.1		c.6080T>C	p.Phe2027Ser	missense	Exon 44 of 44	ENSP00000591614.1
	NUP205	ENST00000921547.1		c.6068T>C	p.Phe2023Ser	missense	Exon 44 of 44	ENSP00000591606.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000827 AC: 2 AN: 241898 AF XY: 0.00000762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1453290 Hom.: 0 Cov.: 30 AF XY: 0.00000968 AC XY: 7 AN XY: 723136

African (AFR) AF: 0.00 AC: 0 AN: 32752

American (AMR) AF: 0.00 AC: 0 AN: 42446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 38864

South Asian (SAS) AF: 0.00 AC: 0 AN: 84842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109322

Other (OTH) AF: 0.00 AC: 0 AN: 59982

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Nephrotic syndrome, type 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.2	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		1.0
MutPred		0.60		Gain of disorder (P = 0.0028)
MVP		0.77
MPC		1.1
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.87
gMVP		0.90
Mutation Taster		=27/73	disease causing (ClinVar)

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: rs869312984; hg19: chr7-135333249;