NM_002484.4:c.754G>A

Variant names:

• chr16-10761793-G-A
• rs144134176
• NM_002484.4:c.754G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002484.4(NUBP1):​c.754G>A​(p.Ala252Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: NUBP1 NM_002484.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.69
• Publications: 3 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]

TVP23A (HGNC:20398): (trans-golgi network vesicle protein 23 homolog A) This gene encodes a membrane protein associated with the Golgi apparatus, which plays a crucial role in intracellular vesicular transport. The encoded protein is likely associated with the late (trans) Golgi compartments, which are involved in the delivery of secretory and membrane proteins to the endosome, lysosome or the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.754G>A	p.Ala252Thr	missense	Exon 9 of 11	NP_002475.2	P53384-1
	NUBP1	NM_001278506.2		c.721G>A	p.Ala241Thr	missense	Exon 8 of 10	NP_001265435.1	P53384-2
	NUBP1	NM_001323595.2		c.754G>A	p.Ala252Thr	missense	Exon 9 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.754G>A	p.Ala252Thr	missense	Exon 9 of 11	ENSP00000283027.5	P53384-1
	NUBP1	ENST00000433392.6	TSL:1	c.721G>A	p.Ala241Thr	missense	Exon 8 of 10	ENSP00000409654.2	P53384-2
	NUBP1	ENST00000571790.5	TSL:1	n.777G>A		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251432 AF XY: 0.000125

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000123 AC: 180 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 85 AN XY: 727188

African (AFR) AF: 0.000986 AC: 33 AN: 33476

American (AMR) AF: 0.000224 AC: 10 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000115 AC: 128 AN: 1111960

Other (OTH) AF: 0.000132 AC: 8 AN: 60386

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74438

African (AFR) AF: 0.00108 AC: 45 AN: 41560

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000204 Hom.: 0

Bravo AF: 0.000295

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000683 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

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	0.33
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.81
MVP		0.60
MPC		0.15
ClinPred		0.45	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.81
Mutation Taster		=34/66	disease causing

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: rs144134176; hg19: chr16-10855650;