Variant 12-102076854-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024057.4(NUP37):c.723-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,607,552 control chromosomes in the GnomAD database, including 671 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 144 hom., cov: 32)

Exomes 𝑓: 0.024 ( 527 hom. )

Consequence

NUP37
NM_024057.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0009312

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59

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]

NUP37 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-102076854-G-T is Benign according to our data. Variant chr12-102076854-G-T is described in ClinVar as [Benign]. Clinvar id is 3042298.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP37	NM_024057.4 linkuse as main transcript	c.723-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000552283.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP37	ENST00000552283.6 linkuse as main transcript	c.723-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_024057.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5682

AN:

152142

Hom.:

144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0686

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0227

AC:

5607

AN:

246872

Hom.:

106

AF XY:

0.0214

AC XY:

2851

AN XY:

133370

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.0179

Gnomad ASJ exome

AF:

0.0268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00324

Gnomad FIN exome

AF:

0.0364

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0241

AC:

35014

AN:

1455292

Hom.:

527

Cov.:

AF XY:

0.0232

AC XY:

16828

AN XY:

724082

show subpopulations

Gnomad4 AFR exome

AF:

0.0660

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00343

Gnomad4 FIN exome

AF:

0.0373

Gnomad4 NFE exome

AF:

0.0247

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0374

AC:

5687

AN:

152260

Hom.:

144

Cov.:

AF XY:

0.0373

AC XY:

2779

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0686

Gnomad4 AMR

AF:

0.0275

Gnomad4 ASJ

AF:

0.0309

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0291

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NUP37-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 18, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

Cadd

Benign

9.4

Dann

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00093

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: -7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over