chr16-1788639-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012225.4(NUBP2):​c.741T>G​(p.Pro247Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NUBP2 NM_012225.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.338 with no splicing effect.

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.741T>G	p.Pro247Pro	synonymous	Exon 7 of 7	NP_036357.1
	NUBP2	NM_001284502.2		c.295T>G	p.Trp99Gly	missense	Exon 6 of 6	NP_001271431.1
	NUBP2	NM_001284501.2		c.561T>G	p.Pro187Pro	synonymous	Exon 8 of 8	NP_001271430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	ENST00000262302.14	TSL:1 MANE Select	c.741T>G	p.Pro247Pro	synonymous	Exon 7 of 7	ENSP00000262302.9
	NUBP2	ENST00000565987.5	TSL:5	c.561T>G	p.Pro187Pro	synonymous	Exon 8 of 8	ENSP00000455896.1
	NUBP2	ENST00000568706.1	TSL:2	c.318T>G	p.Pro106Pro	synonymous	Exon 6 of 6	ENSP00000460079.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458922 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 725766

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111364

Other (OTH) AF: 0.00 AC: 0 AN: 60306

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.34

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;