2-27439857-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_013392.4(NRBP1):​c.995C>T​(p.Ser332Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,026 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NRBP1
NM_013392.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18460658).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRBP1NM_013392.4 linkc.995C>T p.Ser332Leu missense_variant Exon 11 of 18 ENST00000379852.8 NP_037524.1 Q9UHY1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRBP1ENST00000379852.8 linkc.995C>T p.Ser332Leu missense_variant Exon 11 of 18 1 NM_013392.4 ENSP00000369181.3 Q9UHY1
NRBP1ENST00000379863.7 linkc.1019C>T p.Ser340Leu missense_variant Exon 12 of 19 5 ENSP00000369192.3 F8W6G1
NRBP1ENST00000233557.7 linkc.995C>T p.Ser332Leu missense_variant Exon 12 of 19 2 ENSP00000233557.3 Q9UHY1
NRBP1ENST00000460499.5 linkn.1505C>T non_coding_transcript_exon_variant Exon 4 of 11 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.995C>T (p.S332L) alteration is located in exon 11 (coding exon 10) of the NRBP1 gene. This alteration results from a C to T substitution at nucleotide position 995, causing the serine (S) at amino acid position 332 to be replaced by a leucine (L). 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
0.19
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;T
Eigen
Benign
0.092
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Pathogenic
0.97
.;D;D
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.40
N;N;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-4.2
D;D;D
REVEL
Benign
0.090
Sift
Benign
0.051
T;T;D
Sift4G
Benign
0.072
T;T;T
Polyphen
0.11
B;B;B
Vest4
0.21
MutPred
0.56
.;.;Loss of ubiquitination at K342 (P = 0.1343);
MVP
0.26
MPC
0.54
ClinPred
0.97
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.35

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: rs1664457425; hg19: chr2-27662724; COSMIC: COSV51994960; COSMIC: COSV51994960; API