chr6-17624573-T-C

Position:

• chr6-17624573-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.019 (97 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (101 hom.)
• Consequence: NUP153 NM_005124.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.291

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 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/exons	MANE	Protein	UniProt
NUP153	NM_005124.4	c.4162A>G	p.Thr1388Ala	missense_variant	20/22	ENST00000262077.3	NP_005115.2
NUP153	NM_001278209.2	c.4255A>G	p.Thr1419Ala	missense_variant	21/23		NP_001265138.1
NUP153	NM_001278210.2	c.4036A>G	p.Thr1346Ala	missense_variant	19/21		NP_001265139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP153	ENST00000262077.3	c.4162A>G	p.Thr1388Ala	missense_variant	20/22	1	NM_005124.4	ENSP00000262077.3
NUP153	ENST00000613258.4	c.4036A>G	p.Thr1346Ala	missense_variant	19/21	1		ENSP00000478627.1
NUP153	ENST00000537253.5	c.4255A>G	p.Thr1419Ala	missense_variant	21/23	2		ENSP00000444029.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2942 AN: 151262 Hom.: 97 Cov.: 32

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.: 46 AF XY: 0.00384 AC XY: 520 AN XY: 135584

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.: 31 AF XY: 0.00179 AC XY: 1301 AN XY: 727042

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.: 97 Cov.: 32 AF XY: 0.0181 AC XY: 1342 AN XY: 73950

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.: 18

Bravo AF: 0.0223

ESP6500AA AF: 0.0676 AC: 298

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00630 AC: 765

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.77
DEOGEN2	Benign	0.0041	.;.;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.59	T;T;T
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.2	.;.;N
PrimateAI	Benign	0.33	T
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	T
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

Other links and lift over

dbSNP: rs2228379; hg19: chr6-17624804; COSMIC: COSV50459614; COSMIC: COSV50459614;