16-1788639-T-C

Variant names:

• chr16-1788639-T-C
• rs344359
• NM_012225.4:c.741T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012225.4(NUBP2):​c.741T>C​(p.Pro247Pro) variant causes a synonymous 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. 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_012225.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.338 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
NUBP2	NM_012225.4	c.741T>C	p.Pro247Pro	synonymous_variant	Exon 7 of 7	ENST00000262302.14	NP_036357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUBP2	ENST00000262302.14	c.741T>C	p.Pro247Pro	synonymous_variant	Exon 7 of 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

GnomAD2 exomes AF: 0.807 AC: 198173 AN: 245468 AF XY: 0.802

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 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

African (AFR) AF: 0.947 AC: 31681 AN: 33448

American (AMR) AF: 0.817 AC: 36379 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 22123 AN: 26108

East Asian (EAS) AF: 0.683 AC: 27058 AN: 39630

South Asian (SAS) AF: 0.752 AC: 64683 AN: 86036

European-Finnish (FIN) AF: 0.720 AC: 37127 AN: 51594

Middle Eastern (MID) AF: 0.854 AC: 4919 AN: 5760

European-Non Finnish (NFE) AF: 0.820 AC: 910946 AN: 1111302

Other (OTH) AF: 0.813 AC: 49005 AN: 60294

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

African (AFR) AF: 0.939 AC: 39034 AN: 41554

American (AMR) AF: 0.819 AC: 12525 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2950 AN: 3472

East Asian (EAS) AF: 0.724 AC: 3724 AN: 5146

South Asian (SAS) AF: 0.765 AC: 3692 AN: 4824

European-Finnish (FIN) AF: 0.708 AC: 7499 AN: 10592

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55461 AN: 67948

Other (OTH) AF: 0.850 AC: 1793 AN: 2110

Alfa AF: 0.828 Hom.: 66722

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
PhyloP100		-0.34
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: rs344359; hg19: chr16-1838640; COSMIC: COSV107230273; COSMIC: COSV107230273;