16-1788639-T-C

Position:

• chr16-1788639-T-C

Variant summary

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

The NM_001284502.2(NUBP2):​c.295T>C​(p.Trp99Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,610,876 control chromosomes in the GnomAD database, including 536,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict 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 (54077 hom., cov: 34)
  • Exomes 𝑓: 0.81 (481933 hom.)
• Consequence: NUBP2 NM_001284502.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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]

NUBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUBP2	NM_012225.4	c.741T>C	p.Pro247Pro	synonymous_variant	7/7	ENST00000262302.14	NP_036357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUBP2	ENST00000262302.14	c.741T>C	p.Pro247Pro	synonymous_variant	7/7	1	NM_012225.4	ENSP00000262302.9

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127624 AN: 152034 Hom.: 54020 Cov.: 34

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.850

GnomAD3 exomes AF: 0.807 AC: 198173 AN: 245468 Hom.: 80366 AF XY: 0.802 AC XY: 107002 AN XY: 133454

Gnomad AFR exome AF: 0.942

Gnomad AMR exome AF: 0.823

Gnomad ASJ exome AF: 0.850

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.753

Gnomad FIN exome AF: 0.711

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.807

GnomAD4 exome AF: 0.812 AC: 1183921 AN: 1458724 Hom.: 481933 Cov.: 66 AF XY: 0.809 AC XY: 586870 AN XY: 725656

Gnomad4 AFR exome AF: 0.947

Gnomad4 AMR exome AF: 0.817

Gnomad4 ASJ exome AF: 0.847

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.752

Gnomad4 FIN exome AF: 0.720

Gnomad4 NFE exome AF: 0.820

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.840 AC: 127740 AN: 152152 Hom.: 54077 Cov.: 34 AF XY: 0.831 AC XY: 61762 AN XY: 74360

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.850

Alfa AF: 0.823 Hom.: 45790

Bravo AF: 0.856

Asia WGS AF: 0.739 AC: 2572 AN: 3478

EpiCase AF: 0.824

EpiControl AF: 0.829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.54

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: rs344359; hg19: chr16-1838640;