7-135557940-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.-5C>T		5_prime_UTR_variant	1/43	ENST00000285968.11
NUP205	NM_001329434.2	c.-1090C>T		5_prime_UTR_variant	1/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.-5C>T		5_prime_UTR_variant	1/43	1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.9C>T		non_coding_transcript_exon_variant	1/3	4

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

GnomAD3 exomes AF: 0.00808 AC: 2033 AN: 251462 Hom.: 50 AF XY: 0.00912 AC XY: 1239 AN XY: 135904

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 SAS exome AF: 0.0318

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

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0580

Gnomad4 SAS exome AF: 0.0304

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000630

Gnomad4 OTH exome AF: 0.00408

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

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000423 Hom.: 0

Bravo AF: 0.00249

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 28, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	15
Dann	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs80096124; hg19: chr7-135242688; COSMIC: COSV53668290;