6-17624573-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005124.4(NUP153):c.4162A>G(p.Thr1388Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,612,918 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.019 ( 97 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 101 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.291

Variant links:

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]

NUP153 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011480153).

BP6

Variant 6-17624573-T-C is Benign according to our data. Variant chr6-17624573-T-C is described in ClinVar as [Benign]. Clinvar id is 777401.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP153	NM_005124.4 link	c.4162A>G	p.Thr1388Ala	missense_variant	Exon 20 of 22	ENST00000262077.3	NP_005115.2	P49790-1
NUP153	NM_001278209.2 link	c.4255A>G	p.Thr1419Ala	missense_variant	Exon 21 of 23		NP_001265138.1	P49790-3
NUP153	NM_001278210.2 link	c.4036A>G	p.Thr1346Ala	missense_variant	Exon 19 of 21		NP_001265139.1	P49790-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUP153	ENST00000262077.3 link	c.4162A>G	p.Thr1388Ala	missense_variant	Exon 20 of 22	1	NM_005124.4	ENSP00000262077.3	P49790-1
NUP153	ENST00000613258.4 link	c.4036A>G	p.Thr1346Ala	missense_variant	Exon 19 of 21	1		ENSP00000478627.1	P49790-2
NUP153	ENST00000537253.5 link	c.4255A>G	p.Thr1419Ala	missense_variant	Exon 21 of 23	2		ENSP00000444029.1	P49790-3

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2942

AN:

151262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0674

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00889

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:

0.000177

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00524

AC:

1316

AN:

250932

Hom.:

AF XY:

0.00384

AC XY:

520

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.0715

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00203

AC:

2963

AN:

1461538

Hom.:

101

Cov.:

AF XY:

0.00179

AC XY:

1301

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0723

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00467

GnomAD4 genome

AF:

0.0195

AC:

2948

AN:

151380

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1342

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.0673

Gnomad4 AMR

AF:

0.00887

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00787

Hom.:

Bravo

AF:

0.0223

ESP6500AA

AF:

0.0676

AC:

298

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00630

AC:

765

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0041

.;.;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.2

.;.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.42

.;N;N

REVEL

Benign

0.075

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.89

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.084

MVP

0.21

MPC

0.032

ClinPred

0.0020

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.020

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over