Variant 19-48919250-G-T 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.966G>T(p.Gln322His) variant causes a missense change. The variant allele was found at a frequency of 0.000364 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

NUCB1
NM_006184.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

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:

Genome browser will be placed here

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=0.0843015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB1	NM_006184.6 link	c.966G>T	p.Gln322His	missense_variant	10/13	ENST00000405315.9	NP_006175.2	Q02818A8K7Q1
NUCB1	XM_017026845.2 link	c.966G>T	p.Gln322His	missense_variant	10/13		XP_016882334.1	Q02818

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9 link	c.966G>T	p.Gln322His	missense_variant	10/13	1	NM_006184.6	ENSP00000385923.3		Q02818

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000283

AC:

AN:

251244

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000564

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000371

AC:

543

AN:

1461702

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

268

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000296

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000512

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

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

Sep 27, 2021

The c.966G>T (p.Q322H) alteration is located in exon 10 (coding exon 9) of the NUCB1 gene. This alteration results from a G to T substitution at nucleotide position 966, causing the glutamine (Q) at amino acid position 322 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

0.18

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

D;.

M_CAP

Benign

0.052

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.088

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.87

P;P

Vest4

0.32

MutPred

0.20

Loss of disorder (P = 0.2146);Loss of disorder (P = 0.2146);

MVP

0.45

MPC

0.59

ClinPred

0.082

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.25

gMVP

0.47

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

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