16-1785392-A-G

Variant names:

• chr16-1785392-A-G
• rs2575352
• NM_012225.4:c.17-1145A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012225.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	NM_012225.4	MANE Select	c.17-1145A>G		intron	N/A	NP_036357.1
	NUBP2	NM_001284502.2		c.-208-1145A>G		intron	N/A	NP_001271431.1
	NUBP2	NM_001284501.2		c.-164-1145A>G		intron	N/A	NP_001271430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	ENST00000262302.14	TSL:1 MANE Select	c.17-1145A>G		intron	N/A	ENSP00000262302.9
	NUBP2	ENST00000563821.1	TSL:6	n.682A>G		non_coding_transcript_exon	Exon 1 of 1
	NUBP2	ENST00000568610.2	TSL:5	n.742A>G		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.933 AC: 19320 AN: 20708

American (AMR) AF: 0.820 AC: 8711 AN: 10620

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 7825 AN: 9174

East Asian (EAS) AF: 0.745 AC: 8353 AN: 11208

South Asian (SAS) AF: 0.762 AC: 41998 AN: 55146

European-Finnish (FIN) AF: 0.734 AC: 6215 AN: 8466

Middle Eastern (MID) AF: 0.849 AC: 1890 AN: 2226

European-Non Finnish (NFE) AF: 0.831 AC: 716697 AN: 862180

Other (OTH) AF: 0.820 AC: 29530 AN: 36030

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

African (AFR) AF: 0.924 AC: 38408 AN: 41570

American (AMR) AF: 0.821 AC: 12559 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2970 AN: 3472

East Asian (EAS) AF: 0.722 AC: 3731 AN: 5170

South Asian (SAS) AF: 0.771 AC: 3720 AN: 4824

European-Finnish (FIN) AF: 0.712 AC: 7530 AN: 10580

Middle Eastern (MID) AF: 0.894 AC: 261 AN: 292

European-Non Finnish (NFE) AF: 0.826 AC: 56193 AN: 68012

Other (OTH) AF: 0.850 AC: 1799 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.30
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2575352; hg19: chr16-1835393;