11-47779171-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_015231.3(NUP160):c.4143A>G(p.Lys1381=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,612,166 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (69 hom.)
• Consequence: NUP160 NM_015231.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.466

Genes affected

NUP160 (HGNC:18017): (nucleoporin 160) A structural constituent of nuclear pore. Involved in mRNA export from nucleus and nephron development. Part of nuclear pore outer ring. Colocalizes with kinetochore. Implicated in nephrotic syndrome type 19. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-47779171-T-C is Benign according to our data. Variant chr11-47779171-T-C is described in ClinVar as [Benign]. Clinvar id is 790091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.466 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0168 (2557/152298) while in subpopulation AFR AF= 0.0465 (1931/41556). AF 95% confidence interval is 0.0447. There are 44 homozygotes in gnomad4. There are 1252 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP160	NM_015231.3	c.4143A>G	p.Lys1381=	synonymous_variant	36/36	ENST00000378460.7
NUP160	NR_134636.3	n.4190A>G		non_coding_transcript_exon_variant	36/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP160	ENST00000378460.7	c.4143A>G	p.Lys1381=	synonymous_variant	36/36	1	NM_015231.3	P1
NUP160	ENST00000694866.1	c.4245A>G	p.Lys1415=	synonymous_variant	36/36
NUP160	ENST00000530326.5	c.3884-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2555 AN: 152180 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.00955

GnomAD3 exomes AF: 0.00770 AC: 1931 AN: 250732 Hom.: 25 AF XY: 0.00669 AC XY: 907 AN XY: 135592

Gnomad AFR exome AF: 0.0481

Gnomad AMR exome AF: 0.00345

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000623

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.00568

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00433 AC: 6317 AN: 1459868 Hom.: 69 Cov.: 29 AF XY: 0.00422 AC XY: 3067 AN XY: 726362

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00318

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000650

Gnomad4 FIN exome AF: 0.0135

Gnomad4 NFE exome AF: 0.00302

Gnomad4 OTH exome AF: 0.00622

GnomAD4 genome AF: 0.0168 AC: 2557 AN: 152298 Hom.: 44 Cov.: 32 AF XY: 0.0168 AC XY: 1252 AN XY: 74462

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.0116 Hom.: 18

Bravo AF: 0.0167

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.00469

EpiControl AF: 0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

NUP160-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.79

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: rs56962998; hg19: chr11-47800723;