6-17706293-C-T

Position:

• chr6-17706293-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005124.4(NUP153):​c.95G>A​(p.Gly32Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,613,470 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (61 hom.)
• Consequence: NUP153 NM_005124.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.14

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-AS1 (HGNC:55217): (NUP153 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006336063).
• BP6: Variant 6-17706293-C-T is Benign according to our data. Variant chr6-17706293-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 776 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP153	NM_005124.4	c.95G>A	p.Gly32Glu	missense_variant	1/22	ENST00000262077.3	NP_005115.2
NUP153	NM_001278209.2	c.95G>A	p.Gly32Glu	missense_variant	1/23		NP_001265138.1
NUP153	NM_001278210.2	c.95G>A	p.Gly32Glu	missense_variant	1/21		NP_001265139.1
NUP153-AS1	NR_134616.1	n.164C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP153	ENST00000262077.3	c.95G>A	p.Gly32Glu	missense_variant	1/22	1	NM_005124.4	ENSP00000262077.3
NUP153	ENST00000613258.4	c.95G>A	p.Gly32Glu	missense_variant	1/21	1		ENSP00000478627.1
NUP153	ENST00000537253.5	c.95G>A	p.Gly32Glu	missense_variant	1/23	2		ENSP00000444029.1
NUP153-AS1	ENST00000606771.2	n.200C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152234 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00830

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00522 AC: 1304 AN: 249970 Hom.: 6 AF XY: 0.00513 AC XY: 694 AN XY: 135348

Gnomad AFR exome AF: 0.000929

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00825

Gnomad NFE exome AF: 0.00843

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00817 AC: 11939 AN: 1461118 Hom.: 61 Cov.: 31 AF XY: 0.00787 AC XY: 5722 AN XY: 726922

Gnomad4 AFR exome AF: 0.000927

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00797

Gnomad4 NFE exome AF: 0.00978

Gnomad4 OTH exome AF: 0.00597

GnomAD4 genome AF: 0.00509 AC: 776 AN: 152352 Hom.: 4 Cov.: 33 AF XY: 0.00513 AC XY: 382 AN XY: 74504

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00385

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.00831

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00749 Hom.: 8

Bravo AF: 0.00445

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00919 AC: 79

ExAC AF: 0.00521 AC: 632

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00780

EpiControl AF: 0.00694

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 09, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	NUP153: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;.;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.88	D;D;D
MetaRNN	Benign	0.0063	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.97	.;N;N
REVEL	Benign	0.055
Sift	Uncertain	0.015	.;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.70	.;.;P
Vest4		0.29
MVP		0.15
MPC		0.038
ClinPred		0.050	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.20
gMVP		0.31

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: rs61746226; hg19: chr6-17706524; COSMIC: COSV100020978;