7-135571133-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_015135.3(NUP205):​c.57C>T​(p.Asp19Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NUP205 NM_015135.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 7-135571133-C-T is Benign according to our data. Variant chr7-135571133-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2889395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.26 with no splicing effect.

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>T	p.Asp19Asp	synonymous	Exon 2 of 43	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-1029C>T		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>T	p.Asp19Asp	synonymous	Exon 2 of 43	ENSP00000285968.6	Q92621
	NUP205	ENST00000921555.1		c.153C>T	p.Asp51Asp	synonymous	Exon 3 of 44	ENSP00000591614.1
	NUP205	ENST00000921547.1		c.57C>T	p.Asp19Asp	synonymous	Exon 2 of 44	ENSP00000591606.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399832 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 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: 0.0000586 AC: 2 AN: 34150

South Asian (SAS) AF: 0.00 AC: 0 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: 0.0000175 AC: 1 AN: 57194

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely 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	-0.36
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		2.3

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;