Variant chr19-48913096-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006184.6(NUCB1):c.566G>A(p.Arg189His) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

NUCB1
NM_006184.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Variant links:

Genes affected

NUCB1 (HGNC:8043): (nucleobindin 1) This gene encodes a member of a small calcium-binding EF-hand protein family. The encoded protein is thought to have a key role in Golgi calcium homeostasis and Ca(2+)-regulated signal transduction events. [provided by RefSeq, Jun 2010]

NUCB1 links:

NUCB1-AS1 (HGNC:40419): (NUCB1 antisense RNA 1)

NUCB1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07399711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUCB1	NM_006184.6 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	6/13	ENST00000405315.9	NP_006175.2
NUCB1-AS1	NR_046633.1 linkuse as main transcript	n.189-1922C>T		intron_variant, non_coding_transcript_variant
NUCB1	XM_017026845.2 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	6/13		XP_016882334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	6/13	1	NM_006184.6	ENSP00000385923	P2
NUCB1-AS1	ENST00000416432.1 linkuse as main transcript	n.189-1922C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251426

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000889

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2022

The c.566G>A (p.R189H) alteration is located in exon 6 (coding exon 5) of the NUCB1 gene. This alteration results from a G to A substitution at nucleotide position 566, causing the arginine (R) at amino acid position 189 to be replaced by a histidine (H). 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

Benign

0.094

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.043

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.95

D;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.87

N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.10

T;T;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.84

P;P;.

Vest4

0.31

MutPred

0.18

Loss of MoRF binding (P = 0.0331);Loss of MoRF binding (P = 0.0331);Loss of MoRF binding (P = 0.0331);

MVP

0.46

MPC

0.56

ClinPred

0.094

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.23

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

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