6-17632830-C-A

Variant names:

• chr6-17632830-C-A
• rs2274136
• NM_005124.4:c.2479G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005124.4(NUP153):​c.2479G>T​(p.Ala827Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUP153 NM_005124.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 38 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08268002).

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.2479G>T	p.Ala827Ser	missense	Exon 17 of 22	NP_005115.2
	NUP153	NM_001278209.2		c.2572G>T	p.Ala858Ser	missense	Exon 18 of 23	NP_001265138.1
	NUP153	NM_001278210.2		c.2353G>T	p.Ala785Ser	missense	Exon 16 of 21	NP_001265139.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP153	ENST00000262077.3	TSL:1 MANE Select	c.2479G>T	p.Ala827Ser	missense	Exon 17 of 22	ENSP00000262077.3
	NUP153	ENST00000613258.4	TSL:1	c.2353G>T	p.Ala785Ser	missense	Exon 16 of 21	ENSP00000478627.1
	NUP153	ENST00000537253.5	TSL:2	c.2572G>T	p.Ala858Ser	missense	Exon 18 of 23	ENSP00000444029.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 145950 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402862 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 698586

African (AFR) AF: 0.00 AC: 0 AN: 30608

American (AMR) AF: 0.00 AC: 0 AN: 33972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23734

East Asian (EAS) AF: 0.00 AC: 0 AN: 39080

South Asian (SAS) AF: 0.00 AC: 0 AN: 79558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5080

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086344

Other (OTH) AF: 0.00 AC: 0 AN: 57720

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 145950 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 70544

African (AFR) AF: 0.00 AC: 0 AN: 39226

American (AMR) AF: 0.00 AC: 0 AN: 14676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 4998

South Asian (SAS) AF: 0.00 AC: 0 AN: 4624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67120

Other (OTH) AF: 0.00 AC: 0 AN: 1982

Alfa AF: 0.00 Hom.: 133101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.073	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.29
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.020
Sift	Benign	0.31	T
Sift4G	Benign	0.26	T
Polyphen		0.0040	B
Vest4		0.15
MutPred		0.27		Gain of phosphorylation at A827 (P = 0.0055)
MVP		0.25
MPC		0.036
ClinPred		0.37	T
GERP RS		1.1
Varity_R		0.022
gMVP		0.21
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2274136; hg19: chr6-17633061;