NM_024057.4:c.-66+297C>G

Variant names:

• chr12-102119753-G-C
• rs2292303
• NM_024057.4:c.-66+297C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024057.4(NUP37):​c.-66+297C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 152,230 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (398 hom., cov: 32)
• Consequence: NUP37 NM_024057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP37	NM_024057.4	MANE Select	c.-66+297C>G		intron	N/A	NP_076962.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP37	ENST00000552283.6	TSL:5 MANE Select	c.-66+297C>G		intron	N/A	ENSP00000448054.1
	NUP37	ENST00000551200.5	TSL:1	n.42+297C>G		intron	N/A
	NUP37	ENST00000915157.1		c.-66+297C>G		intron	N/A	ENSP00000585216.1

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5398 AN: 152112 Hom.: 394 Cov.: 32

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0416

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0355 AC: 5410 AN: 152230 Hom.: 398 Cov.: 32 AF XY: 0.0407 AC XY: 3029 AN XY: 74432

African (AFR) AF: 0.00628 AC: 261 AN: 41536

American (AMR) AF: 0.0984 AC: 1504 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.299 AC: 1544 AN: 5168

South Asian (SAS) AF: 0.0601 AC: 290 AN: 4822

European-Finnish (FIN) AF: 0.0787 AC: 835 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 879 AN: 68020

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0236 Hom.: 156

Bravo AF: 0.0369

Asia WGS AF: 0.198 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.35
PhyloP100		0.23
PromoterAI		-0.055	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2292303; hg19: chr12-102513531;