6-17625858-G-T

Variant names:

• chr6-17625858-G-T
• rs755579906
• NM_005124.4:c.3851C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005124.4(NUP153):​c.3851C>A​(p.Thr1284Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NUP153 NM_005124.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17777771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP153	NM_005124.4	c.3851C>A	p.Thr1284Asn	missense_variant	Exon 19 of 22	ENST00000262077.3	NP_005115.2
NUP153	NM_001278209.2	c.3944C>A	p.Thr1315Asn	missense_variant	Exon 20 of 23		NP_001265138.1
NUP153	NM_001278210.2	c.3725C>A	p.Thr1242Asn	missense_variant	Exon 18 of 21		NP_001265139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP153	ENST00000262077.3	c.3851C>A	p.Thr1284Asn	missense_variant	Exon 19 of 22	1	NM_005124.4	ENSP00000262077.3
NUP153	ENST00000613258.4	c.3725C>A	p.Thr1242Asn	missense_variant	Exon 18 of 21	1		ENSP00000478627.1
NUP153	ENST00000537253.5	c.3944C>A	p.Thr1315Asn	missense_variant	Exon 20 of 23	2		ENSP00000444029.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251200 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0096	.;.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;.;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.013	.;D;T
Sift4G	Uncertain	0.043	D;T;T
Polyphen		0.80	.;.;P
Vest4		0.18
MutPred		0.14		.;.;Loss of glycosylation at T1284 (P = 0.0314);
MVP		0.30
MPC		0.036
ClinPred		0.41	T
GERP RS		5.8
Varity_R		0.050
gMVP		0.20

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: rs755579906; hg19: chr6-17626089;