2-27433398-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013392.4(NRBP1):​c.125C>G​(p.Ser42Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,614,236 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: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

NRBP1
NM_013392.4 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66
Variant links:
Genes affected
NRBP1 (HGNC:7993): (nuclear receptor binding protein 1) Predicted to enable protein homodimerization activity. Involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in endomembrane system. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.050235838).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRBP1NM_013392.4 linkc.125C>G p.Ser42Cys missense_variant Exon 2 of 18 ENST00000379852.8 NP_037524.1 Q9UHY1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRBP1ENST00000379852.8 linkc.125C>G p.Ser42Cys missense_variant Exon 2 of 18 1 NM_013392.4 ENSP00000369181.3 Q9UHY1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000961
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000115
AC:
29
AN:
251452
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00158
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.0000289
AC XY:
21
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000932
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152352
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000963
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000741
AC:
9
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.125C>G (p.S42C) alteration is located in exon 2 (coding exon 1) of the NRBP1 gene. This alteration results from a C to G substitution at nucleotide position 125, causing the serine (S) at amino acid position 42 to be replaced by a cysteine (C). 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
0.088
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.29
T;T;T;.;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
.;D;D;D;D
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.050
T;T;T;T;T
MetaSVM
Pathogenic
1.2
D
MutationAssessor
Benign
0.69
N;N;.;.;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-2.5
N;N;N;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0060
D;D;D;D;D
Sift4G
Uncertain
0.055
T;T;T;T;D
Polyphen
0.41
B;B;P;.;.
Vest4
0.17
MutPred
0.25
Loss of phosphorylation at S42 (P = 0.0013);Loss of phosphorylation at S42 (P = 0.0013);Loss of phosphorylation at S42 (P = 0.0013);Loss of phosphorylation at S42 (P = 0.0013);Loss of phosphorylation at S42 (P = 0.0013);
MVP
0.60
MPC
1.4
ClinPred
0.15
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.14

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.

Other links and lift over

dbSNP: rs563642807; hg19: chr2-27656265; API