Genetic Variant NUBP1:p.Gly251Gly (chr16-10761792-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_002484.4(NUBP1):c.753C>T(p.Gly251Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,614,056 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 1 hom. )

Consequence

NUBP1
NM_002484.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.14

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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-10761792-C-T is Benign according to our data. Variant chr16-10761792-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646204.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUBP1	NM_002484.4 link	c.753C>T	p.Gly251Gly	synonymous_variant	Exon 9 of 11	ENST00000283027.10	NP_002475.2	P53384-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUBP1	ENST00000283027.10 link	c.753C>T	p.Gly251Gly	synonymous_variant	Exon 9 of 11	1	NM_002484.4	ENSP00000283027.5		P53384-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000620

AC:

156

AN:

251436

AF XY:

0.000648

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000888

AC:

1298

AN:

1461766

Hom.:

Cov.:

AF XY:

0.000898

AC XY:

653

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.0000671

AC:

AN:

44720

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26132

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.0000464

AC:

AN:

86254

Gnomad4 FIN exome

AF:

0.000112

AC:

AN:

53406

Gnomad4 NFE exome

AF:

0.00111

AC:

1235

AN:

1111922

Gnomad4 Remaining exome

AF:

0.000480

AC:

AN:

60392

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152290

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000529

AC:

0.000529381

AN:

0.000529381

Gnomad4 AMR

AF:

0.0000654

AC:

0.0000653851

AN:

0.0000653851

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288018

AN:

0.000288018

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.000188

AC:

0.000188288

AN:

0.000188288

Gnomad4 NFE

AF:

0.00129

AC:

0.00129358

AN:

0.00129358

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.000552

EpiCase

AF:

0.00115

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NUBP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.14

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over