16-10744035-G-A

Variant names:

• chr16-10744035-G-A
• rs752879211
• NM_002484.4:c.94G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002484.4(NUBP1):​c.94G>A​(p.Ala32Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000127 in 1,580,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A32P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: NUBP1 NM_002484.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

Genes affected

NUBP1 (HGNC:8041): (NUBP iron-sulfur cluster assembly factor 1, cytosolic) NUBP1 is a member of the NUBP/MRP subfamily of ATP-binding proteins (Nakashima et al., 1999 [PubMed 10486206]).[supplied by OMIM, Mar 2008]

ENSG00000289073 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38770366).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002484.4. 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
	NUBP1	NM_002484.4	MANE Select	c.94G>A	p.Ala32Thr	missense	Exon 2 of 11	NP_002475.2	P53384-1
	NUBP1	NM_001278506.2		c.94G>A	p.Ala32Thr	missense	Exon 2 of 10	NP_001265435.1	P53384-2
	NUBP1	NM_001323595.2		c.94G>A	p.Ala32Thr	missense	Exon 2 of 10	NP_001310524.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP1	ENST00000283027.10	TSL:1 MANE Select	c.94G>A	p.Ala32Thr	missense	Exon 2 of 11	ENSP00000283027.5	P53384-1
	NUBP1	ENST00000433392.6	TSL:1	c.94G>A	p.Ala32Thr	missense	Exon 2 of 10	ENSP00000409654.2	P53384-2
	NUBP1	ENST00000571790.5	TSL:1	n.117G>A		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000489 AC: 1 AN: 204456 AF XY: 0.00000888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000105

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000133 AC: 19 AN: 1428566 Hom.: 0 Cov.: 32 AF XY: 0.0000113 AC XY: 8 AN XY: 710106

African (AFR) AF: 0.0000635 AC: 2 AN: 31476

American (AMR) AF: 0.00 AC: 0 AN: 35990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24918

East Asian (EAS) AF: 0.00 AC: 0 AN: 37888

South Asian (SAS) AF: 0.00 AC: 0 AN: 81122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1101276

Other (OTH) AF: 0.0000170 AC: 1 AN: 58882

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.056	T
Polyphen		0.98	D
Vest4		0.62
MutPred		0.33		Gain of glycosylation at A32 (P = 0.0244)
MVP		0.63
MPC		0.093
ClinPred		0.98	D
GERP RS		4.1
PromoterAI		-0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.71
gMVP		0.56
Mutation Taster		=56/44	polymorphism

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: rs752879211; hg19: chr16-10837892;