Variant 12-102101071-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_024057.4(NUP37):c.315A>G(p.Arg105Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,561,180 control chromosomes in the GnomAD database, including 644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.028 ( 79 hom., cov: 32)

Exomes 𝑓: 0.025 ( 565 hom. )

Consequence

NUP37
NM_024057.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0890

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=-0.48).

BP6

Variant 12-102101071-T-C is Benign according to our data. Variant chr12-102101071-T-C is described in ClinVar as [Benign]. Clinvar id is 3037376.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.089 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0282 (4299/152268) while in subpopulation AFR AF= 0.0331 (1375/41554). AF 95% confidence interval is 0.0316. There are 79 homozygotes in gnomad4. There are 2087 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP37	NM_024057.4 link	c.315A>G	p.Arg105Arg	synonymous_variant	4/10	ENST00000552283.6	NP_076962.2	Q8NFH4
NUP37	XM_047429530.1 link	c.315A>G	p.Arg105Arg	synonymous_variant	4/7		XP_047285486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP37	ENST00000552283.6 link	c.315A>G	p.Arg105Arg	synonymous_variant	4/10	5	NM_024057.4	ENSP00000448054.1		Q8NFH4

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4294

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0245

AC:

5496

AN:

224202

Hom.:

115

AF XY:

0.0248

AC XY:

3019

AN XY:

121930

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.00800

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.0465

Gnomad NFE exome

AF:

0.0304

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0254

AC:

35790

AN:

1408912

Hom.:

565

Cov.:

AF XY:

0.0254

AC XY:

17821

AN XY:

700332

show subpopulations

Gnomad4 AFR exome

AF:

0.0312

Gnomad4 AMR exome

AF:

0.00949

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0194

Gnomad4 FIN exome

AF:

0.0458

Gnomad4 NFE exome

AF:

0.0266

Gnomad4 OTH exome

AF:

0.0223

GnomAD4 genome

AF:

0.0282

AC:

4299

AN:

152268

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2087

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0331

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.0444

Gnomad4 NFE

AF:

0.0290

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0296

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.00982

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NUP37-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 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

-0.48

CADD

Benign

7.8

DANN

Benign

0.67

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.

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