rs10507142

chr12-102098235-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NUP37	NM_024057.4	c.449+871A>C		intron_variant		ENST00000552283.6
NUP37	XM_047429530.1	c.449+871A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP37	ENST00000552283.6	c.449+871A>C		intron_variant		5	NM_024057.4	P1

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

Gnomad4 AFR AF: 0.00633

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0421

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

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

Other links and lift over

dbSNP: rs10507142; hg19: chr12-102492013;