16-10768011-G-C

Variant names:

• chr16-10768011-G-C
• NM_002484.4:c.883G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001323596.2(NUBP1):​c.780G>C​(p.Ter260Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUBP1 NM_001323596.2 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15

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
• PM4: Stoplost variant in NM_001323596.2 Downstream stopcodon found after 266 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUBP1	NM_002484.4	c.883G>C	p.Ala295Pro	missense_variant	Exon 10 of 11	ENST00000283027.10	NP_002475.2
TVP23A	NM_001079512.4	c.*1091C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000299866.13	NP_001072980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUBP1	ENST00000283027.10	c.883G>C	p.Ala295Pro	missense_variant	Exon 10 of 11	1	NM_002484.4	ENSP00000283027.5
TVP23A	ENST00000299866	c.*1091C>G		3_prime_UTR_variant	Exon 8 of 8	2	NM_001079512.4	ENSP00000299866.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.883G>C (p.A295P) alteration is located in exon 10 (coding exon 10) of the NUBP1 gene. This alteration results from a G to C substitution at nucleotide position 883, causing the alanine (A) at amino acid position 295 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Benign	0.80
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.049	D;D
Polyphen		0.74	P;B
Vest4		0.67
MutPred		0.64		Gain of disorder (P = 0.0546);.;
MVP		0.36
MPC		0.085
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.75
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-10861868;