6-17665126-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005124.4(NUP153):​c.1215+113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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>A		intron	N/A	NP_005115.2
	NUP153	NM_001278209.2		c.1215+113T>A		intron	N/A	NP_001265138.1
	NUP153	NM_001278210.2		c.1215+113T>A		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>A		intron	N/A	ENSP00000262077.3
	NUP153	ENST00000613258.4	TSL:1	c.1215+113T>A		intron	N/A	ENSP00000478627.1
	NUP153	ENST00000537253.5	TSL:2	c.1215+113T>A		intron	N/A	ENSP00000444029.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 484930 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 249346

African (AFR) AF: 0.00 AC: 0 AN: 11696

American (AMR) AF: 0.00 AC: 0 AN: 12902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12172

East Asian (EAS) AF: 0.00 AC: 0 AN: 26238

South Asian (SAS) AF: 0.00 AC: 0 AN: 27224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 338454

Other (OTH) AF: 0.00 AC: 0 AN: 25214

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.80
PhyloP100		1.3
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

Other links and lift over

dbSNP: rs6929659; hg19: chr6-17665357;