chr1-229449164-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018230.3(NUP133):ā€‹c.3207A>Gā€‹(p.Leu1069=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,611,302 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0091 ( 20 hom., cov: 32)
Exomes š‘“: 0.00091 ( 25 hom. )

Consequence

NUP133
NM_018230.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
NUP133 (HGNC:18016): (nucleoporin 133) The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. The nucleoporin protein encoded by this gene displays evolutionarily conserved interactions with other nucleoporins. This protein, which localizes to both sides of the nuclear pore complex at interphase, remains associated with the complex during mitosis and is targeted at early stages to the reforming nuclear envelope. This protein also localizes to kinetochores of mitotic cells. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 1-229449164-T-C is Benign according to our data. Variant chr1-229449164-T-C is described in ClinVar as [Benign]. Clinvar id is 1630526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.08 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1379/152326) while in subpopulation AFR AF= 0.0313 (1303/41568). AF 95% confidence interval is 0.0299. There are 20 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NUP133NM_018230.3 linkuse as main transcriptc.3207A>G p.Leu1069= synonymous_variant 24/26 ENST00000261396.6 NP_060700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUP133ENST00000261396.6 linkuse as main transcriptc.3207A>G p.Leu1069= synonymous_variant 24/261 NM_018230.3 ENSP00000261396 P1
NUP133ENST00000485119.1 linkuse as main transcriptn.573A>G non_coding_transcript_exon_variant 2/23
NUP133ENST00000490352.1 linkuse as main transcriptn.254A>G non_coding_transcript_exon_variant 2/42

Frequencies

GnomAD3 genomes
AF:
0.00904
AC:
1376
AN:
152208
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00353
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00224
AC:
560
AN:
249608
Hom.:
11
AF XY:
0.00150
AC XY:
202
AN XY:
134958
show subpopulations
Gnomad AFR exome
AF:
0.0314
Gnomad AMR exome
AF:
0.00102
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000660
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00181
GnomAD4 exome
AF:
0.000908
AC:
1325
AN:
1458976
Hom.:
25
Cov.:
28
AF XY:
0.000805
AC XY:
584
AN XY:
725910
show subpopulations
Gnomad4 AFR exome
AF:
0.0339
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000930
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000991
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
AF:
0.00905
AC:
1379
AN:
152326
Hom.:
20
Cov.:
32
AF XY:
0.00859
AC XY:
640
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0313
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00374
Hom.:
1
Bravo
AF:
0.0109
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
8.1
DANN
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs77677767; hg19: chr1-229584911; API