6-17665126-A-G

Position:

• chr6-17665126-A-G

Variant summary

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

The ENST00000262077.3(NUP153):​c.1215+113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 634,548 control chromosomes in the GnomAD database, including 79,039 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 0.45 (15983 hom., cov: 29)
  • Exomes 𝑓: 0.50 (63056 hom.)
• Consequence: NUP153 ENST00000262077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

NUP153 (HGNC:8062): (nucleoporin 153) Nuclear pore complexes regulate the transport of macromolecules between the nucleus and cytoplasm. They are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. Nucleoporins are glycoproteins found in nuclear pores and contain characteristic pentapeptide XFXFG repeats as well as O-linked N-acetylglucosamine residues oriented towards the cytoplasm. The protein encoded by this gene has three distinct domains: a N-terminal region containing a pore targeting and an RNA-binding domain domain, a central region containing multiple zinc finger motifs, and a C-terminal region containing multiple XFXFG repeats. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP153	NM_005124.4	c.1215+113T>C		intron_variant		ENST00000262077.3	NP_005115.2
NUP153	NM_001278209.2	c.1215+113T>C		intron_variant			NP_001265138.1
NUP153	NM_001278210.2	c.1215+113T>C		intron_variant			NP_001265139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP153	ENST00000262077.3	c.1215+113T>C		intron_variant		1	NM_005124.4	ENSP00000262077	P1
NUP153	ENST00000613258.4	c.1215+113T>C		intron_variant		1		ENSP00000478627
NUP153	ENST00000537253.5	c.1215+113T>C		intron_variant		2		ENSP00000444029

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67472 AN: 150920 Hom.: 15973 Cov.: 29

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.501 AC: 241999 AN: 483514 Hom.: 63056 AF XY: 0.508 AC XY: 126225 AN XY: 248626

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.633

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.447 AC: 67528 AN: 151034 Hom.: 15983 Cov.: 29 AF XY: 0.448 AC XY: 33021 AN XY: 73688

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.513

Alfa AF: 0.436 Hom.: 1830

Bravo AF: 0.450

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6929659; hg19: chr6-17665357; COSMIC: COSV50474273;