chr6-17626050-T-C

Position:

chr6-17626050-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005124.4(NUP153):c.3659A>G(p.Asn1220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,614,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0390

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005307853).

BP6

Variant 6-17626050-T-C is Benign according to our data. Variant chr6-17626050-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2349772.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 112 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP153	NM_005124.4 linkuse as main transcript	c.3659A>G	p.Asn1220Ser	missense_variant	19/22	ENST00000262077.3	NP_005115.2	P49790-1
NUP153	NM_001278209.2 linkuse as main transcript	c.3752A>G	p.Asn1251Ser	missense_variant	20/23		NP_001265138.1	P49790-3
NUP153	NM_001278210.2 linkuse as main transcript	c.3533A>G	p.Asn1178Ser	missense_variant	18/21		NP_001265139.1	P49790-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUP153	ENST00000262077.3 linkuse as main transcript	c.3659A>G	p.Asn1220Ser	missense_variant	19/22	1	NM_005124.4	ENSP00000262077.3	P49790-1
NUP153	ENST00000613258.4 linkuse as main transcript	c.3533A>G	p.Asn1178Ser	missense_variant	18/21	1		ENSP00000478627.1	P49790-2
NUP153	ENST00000537253.5 linkuse as main transcript	c.3752A>G	p.Asn1251Ser	missense_variant	20/23	2		ENSP00000444029.1	P49790-3

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000811

AC:

203

AN:

250340

Hom.:

AF XY:

0.000879

AC XY:

119

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00139

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00120

AC:

1756

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

846

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.000736

AC:

112

AN:

152264

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000716

Hom.:

Bravo

AF:

0.000884

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000898

AC:

109

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

DANN

Benign

0.34

DEOGEN2

Benign

0.012

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.35

.;.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.071

Sift

Benign

0.37

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.21

MVP

0.32

MPC

0.028

ClinPred

0.0072

GERP RS

-5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.068

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