Genetic Variant NM_002484.4:c.502C>G (chr16-10757923-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002484.4(NUBP1):c.502C>G(p.Leu168Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NUBP1
NM_002484.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Publications

0 publications found

Variant links:

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]

NUBP1 links:

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]

TVP23A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUBP1	NM_002484.4	MANE Select	c.502C>G	p.Leu168Val	missense	Exon 7 of 11	NP_002475.2	P53384-1
NUBP1	NM_001278506.2		c.469C>G	p.Leu157Val	missense	Exon 6 of 10	NP_001265435.1	P53384-2
NUBP1	NM_001323595.2		c.502C>G	p.Leu168Val	missense	Exon 7 of 10	NP_001310524.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUBP1	ENST00000283027.10	TSL:1 MANE Select	c.502C>G	p.Leu168Val	missense	Exon 7 of 11	ENSP00000283027.5	P53384-1
NUBP1	ENST00000433392.6	TSL:1	c.469C>G	p.Leu157Val	missense	Exon 6 of 10	ENSP00000409654.2	P53384-2
NUBP1	ENST00000571790.5	TSL:1	n.525C>G		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

3.2

PhyloP100

4.4

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.76

MutPred

0.67

Loss of stability (P = 0.1429)

MVP

0.78

MPC

0.14

ClinPred

0.99

GERP RS

5.1

PromoterAI

0.14

Neutral

(source)

Varity_R

0.70

gMVP

0.77

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over