7-135608380-A-G

Variant names:

• chr7-135608380-A-G
• rs4294134
• NM_015135.3:c.3195+1009A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015135.3(NUP205):​c.3195+1009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,136 control chromosomes in the GnomAD database, including 44,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44686 hom., cov: 31)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP205	NM_015135.3	c.3195+1009A>G		intron_variant	Intron 22 of 42	ENST00000285968.11	NP_055950.2
NUP205	NM_001329434.2	c.2121+1009A>G		intron_variant	Intron 22 of 42		NP_001316363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP205	ENST00000285968.11	c.3195+1009A>G		intron_variant	Intron 22 of 42	1	NM_015135.3	ENSP00000285968.6
NUP205	ENST00000472132.5	c.366+1009A>G		intron_variant	Intron 3 of 4	4		ENSP00000475665.1
NUP205	ENST00000463247.1	n.168+1009A>G		intron_variant	Intron 2 of 5	4		ENSP00000475539.1
NUP205	ENST00000607647.5	n.1473+1009A>G		intron_variant	Intron 9 of 29	5

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115533 AN: 152018 Hom.: 44680 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.760 AC: 115573 AN: 152136 Hom.: 44686 Cov.: 31 AF XY: 0.759 AC XY: 56441 AN XY: 74386

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.772

Alfa AF: 0.827 Hom.: 104087

Bravo AF: 0.739

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.65

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: rs4294134; hg19: chr7-135293128;