rs10507142

Variant names:

• chr12-102098235-T-G
• rs10507142
• NM_024057.4:c.449+871A>C

Variant summary

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

The NM_024057.4(NUP37):​c.449+871A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 152,262 control chromosomes in the GnomAD database, including 384 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 0.035 (384 hom., cov: 32)
• Consequence: NUP37 NM_024057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 1 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP37	NM_024057.4	c.449+871A>C		intron_variant	Intron 5 of 9	ENST00000552283.6	NP_076962.2
NUP37	XM_047429530.1	c.449+871A>C		intron_variant	Intron 5 of 6		XP_047285486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP37	ENST00000552283.6	c.449+871A>C		intron_variant	Intron 5 of 9	5	NM_024057.4	ENSP00000448054.1

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5365 AN: 152144 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.00635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0974

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.0589

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0353 AC: 5377 AN: 152262 Hom.: 384 Cov.: 32 AF XY: 0.0405 AC XY: 3015 AN XY: 74434

African (AFR) AF: 0.00633 AC: 263 AN: 41558

American (AMR) AF: 0.0981 AC: 1500 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1515 AN: 5162

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4820

European-Finnish (FIN) AF: 0.0788 AC: 837 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0129 AC: 879 AN: 68032

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0227 Hom.: 17

Bravo AF: 0.0368

Asia WGS AF: 0.197 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		1.0
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: rs10507142; hg19: chr12-102492013;