16-10761793-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002484.4(NUBP1):​c.754G>T​(p.Ala252Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NUBP1 NM_002484.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.69

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUBP1	NM_002484.4	c.754G>T	p.Ala252Ser	missense_variant	Exon 9 of 11	ENST00000283027.10	NP_002475.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUBP1	ENST00000283027.10	c.754G>T	p.Ala252Ser	missense_variant	Exon 9 of 11	1	NM_002484.4	ENSP00000283027.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251432 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.7	H;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;D
Vest4		0.71
MutPred		0.65		Gain of disorder (P = 0.0144);.;
MVP		0.56
MPC		0.15
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs144134176; hg19: chr16-10855650;