chr7-135557940-C-T

Variant names:

• chr7-135557940-C-T
• rs80096124
• NM_015135.3:c.-5C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_015135.3(NUP205):​c.-5C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,613,584 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (131 hom.)
• Consequence: NUP205 NM_015135.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.424
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-135557940-C-T is Benign according to our data. Variant chr7-135557940-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0561 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.-5C>T		5_prime_UTR	Exon 1 of 43	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-1090C>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.-5C>T		5_prime_UTR	Exon 1 of 43	ENSP00000285968.6	Q92621
	NUP205	ENST00000921555.1		c.-5C>T		5_prime_UTR	Exon 1 of 44	ENSP00000591614.1
	NUP205	ENST00000921547.1		c.-5C>T		5_prime_UTR	Exon 1 of 44	ENSP00000591606.1

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 427 AN: 152196 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00808 AC: 2033 AN: 251462 AF XY: 0.00912

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00361 AC: 5268 AN: 1461270 Hom.: 131 Cov.: 29 AF XY: 0.00439 AC XY: 3193 AN XY: 726996

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0580 AC: 2304 AN: 39694

South Asian (SAS) AF: 0.0304 AC: 2624 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1111462

Other (OTH) AF: 0.00408 AC: 246 AN: 60368

GnomAD4 genome AF: 0.00279 AC: 425 AN: 152314 Hom.: 9 Cov.: 32 AF XY: 0.00341 AC XY: 254 AN XY: 74472

African (AFR) AF: 0.000144 AC: 6 AN: 41562

American (AMR) AF: 0.000261 AC: 4 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5180

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000393 Hom.: 0

Bravo AF: 0.00249

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		0.42
PromoterAI		-0.18	Neutral
Mutation Taster		=300/0	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: rs80096124; hg19: chr7-135242688; COSMIC: COSV53668290;