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12-102118369-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_024057.4(NUP37):c.150G>A(p.Thr50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,612,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

NUP37
NM_024057.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.519
Variant links:
Genes affected
NUP37 (HGNC:29929): (nucleoporin 37) Nuclear pore complexes (NPCs) are used for transporting macromolecules between the cytoplasm and the nucleus. NPCs consist of multiple copies of 30 distinct proteins (nucleoporins), which assemble into biochemically-separable subcomplexes. The protein encoded by this gene is part of a subcomplex (Nup107-160) that is required for proper NPC function as well as for normal kinetochore-microtubule interaction and mitosis. [provided by RefSeq, Dec 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-102118369-C-T is Benign according to our data. Variant chr12-102118369-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.519 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NUP37NM_024057.4 linkuse as main transcriptc.150G>A p.Thr50= synonymous_variant 2/10 ENST00000552283.6
NUP37XM_047429530.1 linkuse as main transcriptc.150G>A p.Thr50= synonymous_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUP37ENST00000552283.6 linkuse as main transcriptc.150G>A p.Thr50= synonymous_variant 2/105 NM_024057.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000230
AC:
35
AN:
151980
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000257
AC:
64
AN:
249478
Hom.:
0
AF XY:
0.000237
AC XY:
32
AN XY:
134914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000878
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000931
Gnomad NFE exome
AF:
0.000469
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000334
AC:
488
AN:
1459908
Hom.:
0
Cov.:
31
AF XY:
0.000343
AC XY:
249
AN XY:
726292
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000113
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000937
Gnomad4 NFE exome
AF:
0.000398
Gnomad4 OTH exome
AF:
0.000381
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000230
AC:
35
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000424
Hom.:
0
Bravo
AF:
0.000234
EpiCase
AF:
0.000218
EpiControl
AF:
0.000415

ClinVar

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

Submissions by phenotype

NUP37-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 12, 2019This 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
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022NUP37: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
4.0
Dann
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs139625051; hg19: chr12-102512147; COSMIC: COSV51839771; COSMIC: COSV51839771; API