16-1788835-C-T

Variant names:

• chr16-1788835-C-T
• rs1065656
• NM_012225.4:c.*121C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284502.2(NUBP2):​c.491C>T​(p.Pro164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000792 in 1,136,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: NUBP2 NM_001284502.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 50 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284502.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	NM_012225.4	MANE Select	c.*121C>T		3_prime_UTR	Exon 7 of 7	NP_036357.1	Q9Y5Y2
	NUBP2	NM_001284502.2		c.491C>T	p.Pro164Leu	missense	Exon 6 of 6	NP_001271431.1
	NUBP2	NM_001284501.2		c.*121C>T		3_prime_UTR	Exon 8 of 8	NP_001271430.1	H3BQR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	ENST00000262302.14	TSL:1 MANE Select	c.*121C>T		3_prime_UTR	Exon 7 of 7	ENSP00000262302.9	Q9Y5Y2
	NUBP2	ENST00000881954.1		c.*121C>T		3_prime_UTR	Exon 7 of 7	ENSP00000552013.1
	NUBP2	ENST00000942968.1		c.*121C>T		3_prime_UTR	Exon 5 of 5	ENSP00000613027.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000792 AC: 9 AN: 1136484 Hom.: 0 Cov.: 15 AF XY: 0.00000902 AC XY: 5 AN XY: 554522

African (AFR) AF: 0.00 AC: 0 AN: 25016

American (AMR) AF: 0.00 AC: 0 AN: 19270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17866

East Asian (EAS) AF: 0.0000301 AC: 1 AN: 33214

South Asian (SAS) AF: 0.00 AC: 0 AN: 56820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3754

European-Non Finnish (NFE) AF: 0.00000887 AC: 8 AN: 901624

Other (OTH) AF: 0.00 AC: 0 AN: 48478

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 1532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.86
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1065656; hg19: chr16-1838836;