6-17699091-G-T

Variant names:

• chr6-17699091-G-T
• rs12199222
• NM_005124.4:c.111+7186C>A

Variant summary

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

The NM_005124.4(NUP153):​c.111+7186C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,948 control chromosomes in the GnomAD database, including 6,214 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 0.28 (6214 hom., cov: 32)
• Consequence: NUP153 NM_005124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770
• Publications: 30 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP153	NM_005124.4	c.111+7186C>A		intron_variant	Intron 1 of 21	ENST00000262077.3	NP_005115.2
NUP153	NM_001278209.2	c.111+7186C>A		intron_variant	Intron 1 of 22		NP_001265138.1
NUP153	NM_001278210.2	c.111+7186C>A		intron_variant	Intron 1 of 20		NP_001265139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP153	ENST00000262077.3	c.111+7186C>A		intron_variant	Intron 1 of 21	1	NM_005124.4	ENSP00000262077.3
NUP153	ENST00000613258.4	c.111+7186C>A		intron_variant	Intron 1 of 20	1		ENSP00000478627.1
NUP153	ENST00000537253.5	c.111+7186C>A		intron_variant	Intron 1 of 22	2		ENSP00000444029.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42947 AN: 151832 Hom.: 6212 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.283 AC: 42974 AN: 151948 Hom.: 6214 Cov.: 32 AF XY: 0.285 AC XY: 21155 AN XY: 74240

African (AFR) AF: 0.267 AC: 11044 AN: 41434

American (AMR) AF: 0.250 AC: 3813 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3466

East Asian (EAS) AF: 0.329 AC: 1705 AN: 5176

South Asian (SAS) AF: 0.165 AC: 796 AN: 4814

European-Finnish (FIN) AF: 0.424 AC: 4469 AN: 10528

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19793 AN: 67940

Other (OTH) AF: 0.242 AC: 510 AN: 2108

Alfa AF: 0.274 Hom.: 19682

Bravo AF: 0.274

Asia WGS AF: 0.235 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.44
PhyloP100		0.77
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: rs12199222; hg19: chr6-17699322;