rs145084636

Variant names:

• chr19-49909616-G-A
• rs145084636
• NM_016553.5:c.192C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49909616-G-A
• chr19-49909616-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_016553.5(NUP62):​c.192C>T​(p.Thr64Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,613,390 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0040 (15 hom.)
• Consequence: NUP62 NM_016553.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 1.84
• Publications: 1 publications found

Genes affected

NUP62 (HGNC:8066): (nucleoporin 62) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform. [provided by RefSeq, Jul 2008]

ENSG00000269179 (HGNC:):

IL4I1 (HGNC:19094): (interleukin 4 induced 1) This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5' UTR with the overlapping NUP62 gene. [provided by RefSeq, Jul 2020]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 19-49909616-G-A is Benign according to our data. Variant chr19-49909616-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 211764.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016553.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP62	NM_016553.5	MANE Select	c.192C>T	p.Thr64Thr	synonymous	Exon 3 of 3	NP_057637.2
	NUP62	NM_001193357.2		c.192C>T	p.Thr64Thr	synonymous	Exon 2 of 2	NP_001180286.1
	NUP62	NM_012346.5		c.192C>T	p.Thr64Thr	synonymous	Exon 2 of 2	NP_036478.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP62	ENST00000352066.8	TSL:1 MANE Select	c.192C>T	p.Thr64Thr	synonymous	Exon 3 of 3	ENSP00000305503.3
	NUP62	ENST00000422090.2	TSL:1	c.192C>T	p.Thr64Thr	synonymous	Exon 2 of 2	ENSP00000407331.1
	NUP62	ENST00000597029.6	TSL:1	c.192C>T	p.Thr64Thr	synonymous	Exon 3 of 3	ENSP00000473192.1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152114 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00425

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00265 AC: 667 AN: 251486 AF XY: 0.00262

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00522

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00400 AC: 5839 AN: 1461158 Hom.: 15 Cov.: 35 AF XY: 0.00388 AC XY: 2821 AN XY: 726872

African (AFR) AF: 0.000299 AC: 10 AN: 33474

American (AMR) AF: 0.000873 AC: 39 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86240

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53420

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.00498 AC: 5535 AN: 1111374

Other (OTH) AF: 0.00252 AC: 152 AN: 60360

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152232 Hom.: 0 Cov.: 31 AF XY: 0.00199 AC XY: 148 AN XY: 74458

African (AFR) AF: 0.000794 AC: 33 AN: 41546

American (AMR) AF: 0.000523 AC: 8 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00425 AC: 289 AN: 67990

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.00299 Hom.: 0

Bravo AF: 0.00226

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00469

EpiControl AF: 0.00486

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Jun 27, 2014

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NUP62-related disorder Benign:1

Jun 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs145084636; hg19: chr19-50412873;