rs10507140

Positions:

• chr12-102078982-C-G
• chr12-102078982-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024057.4(NUP37):​c.541-1479G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 207,800 control chromosomes in the GnomAD database, including 542 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 (386 hom., cov: 32)
  • Exomes 𝑓: 0.038 (156 hom.)
• Consequence: NUP37 NM_024057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP37	NM_024057.4	c.541-1479G>C		intron_variant		ENST00000552283.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP37	ENST00000552283.6	c.541-1479G>C		intron_variant		5	NM_024057.4	P1

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5384 AN: 152104 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.00640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0420

GnomAD4 exome AF: 0.0381 AC: 2116 AN: 55578 Hom.: 156 AF XY: 0.0393 AC XY: 1171 AN XY: 29780

Gnomad4 AFR exome AF: 0.00625

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.00537

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.0448

Gnomad4 FIN exome AF: 0.0638

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0398

GnomAD4 genome AF: 0.0354 AC: 5396 AN: 152222 Hom.: 386 Cov.: 32 AF XY: 0.0407 AC XY: 3028 AN XY: 74422

Gnomad4 AFR AF: 0.00638

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0791

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.0368

Asia WGS AF: 0.197 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.34

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: rs10507140; hg19: chr12-102472760;