6-17665126-A-G

Variant names:

• chr6-17665126-A-G
• rs6929659
• NM_005124.4:c.1215+113T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005124.4(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 NM_005124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005124.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP153	NM_005124.4	MANE Select	c.1215+113T>C		intron	N/A	NP_005115.2
	NUP153	NM_001278209.2		c.1215+113T>C		intron	N/A	NP_001265138.1
	NUP153	NM_001278210.2		c.1215+113T>C		intron	N/A	NP_001265139.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP153	ENST00000262077.3	TSL:1 MANE Select	c.1215+113T>C		intron	N/A	ENSP00000262077.3
	NUP153	ENST00000613258.4	TSL:1	c.1215+113T>C		intron	N/A	ENSP00000478627.1
	NUP153	ENST00000537253.5	TSL:2	c.1215+113T>C		intron	N/A	ENSP00000444029.1

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

African (AFR) AF: 0.320 AC: 3735 AN: 11662

American (AMR) AF: 0.495 AC: 6380 AN: 12878

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 7678 AN: 12132

East Asian (EAS) AF: 0.576 AC: 15054 AN: 26144

South Asian (SAS) AF: 0.672 AC: 18229 AN: 27140

European-Finnish (FIN) AF: 0.361 AC: 10327 AN: 28646

Middle Eastern (MID) AF: 0.702 AC: 1618 AN: 2306

European-Non Finnish (NFE) AF: 0.492 AC: 165921 AN: 337458

Other (OTH) AF: 0.519 AC: 13057 AN: 25148

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

African (AFR) AF: 0.321 AC: 13192 AN: 41114

American (AMR) AF: 0.515 AC: 7806 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2205 AN: 3456

East Asian (EAS) AF: 0.553 AC: 2828 AN: 5118

South Asian (SAS) AF: 0.680 AC: 3264 AN: 4798

European-Finnish (FIN) AF: 0.354 AC: 3638 AN: 10282

Middle Eastern (MID) AF: 0.747 AC: 215 AN: 288

European-Non Finnish (NFE) AF: 0.483 AC: 32738 AN: 67832

Other (OTH) AF: 0.513 AC: 1079 AN: 2102

Alfa AF: 0.431 Hom.: 1870

Bravo AF: 0.450

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.86
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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