Variant 19-48913162-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.632G>A(p.Arg211His) variant causes a missense change. The variant allele was found at a frequency of 0.0000824 in 1,613,646 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: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

NUCB1
NM_006184.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

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 (HGNC:):

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=0.15208516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB1	NM_006184.6 linkuse as main transcript	c.632G>A	p.Arg211His	missense_variant	6/13	ENST00000405315.9	NP_006175.2	Q02818A8K7Q1
NUCB1	XM_017026845.2 linkuse as main transcript	c.632G>A	p.Arg211His	missense_variant	6/13		XP_016882334.1	Q02818
NUCB1-AS1	NR_046633.1 linkuse as main transcript	n.189-1988C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9 linkuse as main transcript	c.632G>A	p.Arg211His	missense_variant	6/13	1	NM_006184.6	ENSP00000385923.3		Q02818

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251036

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000876

AC:

128

AN:

1461600

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Aug 05, 2024

The c.632G>A (p.R211H) 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 632, causing the arginine (R) at amino acid position 211 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

0.083

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;D;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

D;.;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.072

T;T;T

Polyphen

0.023

B;B;.

Vest4

0.30

MutPred

0.26

Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);

MVP

0.52

MPC

0.35

ClinPred

0.14

GERP RS

3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.095

gMVP

0.26

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