16-1785392-A-G

Position:

• chr16-1785392-A-G

Variant summary

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

The NM_012225.4(NUBP2):​c.17-1145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,168,000 control chromosomes in the GnomAD database, including 402,505 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 0.84 (54168 hom., cov: 33)
  • Exomes 𝑓: 0.83 (348337 hom.)
• Consequence: NUBP2 NM_012225.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

NUBP2 (HGNC:8042): (NUBP iron-sulfur cluster assembly factor 2, cytosolic) This gene encodes an adenosine triphosphate (ATP) and metal-binding protein that is required for the assembly of cyotosolic iron-sulfur proteins. The encoded protein functions in a heterotetramer with nucleotide-binding protein 1 (NUBP1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

SPSB3 (HGNC:30629): (splA/ryanodine receptor domain and SOCS box containing 3) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUBP2	NM_012225.4	c.17-1145A>G		intron_variant		ENST00000262302.14	NP_036357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUBP2	ENST00000262302.14	c.17-1145A>G		intron_variant		1	NM_012225.4	ENSP00000262302.9

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127872 AN: 152124 Hom.: 54110 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.827 AC: 840539 AN: 1015758 Hom.: 348337 Cov.: 45 AF XY: 0.825 AC XY: 400065 AN XY: 484696

Gnomad4 AFR exome AF: 0.933

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.853

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.762

Gnomad4 FIN exome AF: 0.734

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.841 AC: 127989 AN: 152242 Hom.: 54168 Cov.: 33 AF XY: 0.832 AC XY: 61892 AN XY: 74434

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.850

Alfa AF: 0.831 Hom.: 7681

Bravo AF: 0.856

Asia WGS AF: 0.739 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2575352; hg19: chr16-1835393;