7-98281908-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015379.5(BRI3):​c.113C>G​(p.Pro38Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000175 in 1,144,966 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: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

BRI3
NM_015379.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92
Variant links:
Genes affected
BRI3 (HGNC:1109): (brain protein I3) Enables identical protein binding activity. Predicted to be located in azurophil granule membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30349278).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRI3NM_015379.5 linkc.113C>G p.Pro38Arg missense_variant Exon 1 of 3 ENST00000297290.4 NP_056194.1 O95415-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRI3ENST00000297290.4 linkc.113C>G p.Pro38Arg missense_variant Exon 1 of 3 1 NM_015379.5 ENSP00000297290.3 O95415-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.000208
AC:
1
AN:
4800
Hom.:
0
AF XY:
0.000350
AC XY:
1
AN XY:
2860
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000300
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000175
AC:
2
AN:
1144966
Hom.:
0
Cov.:
31
AF XY:
0.00000364
AC XY:
2
AN XY:
549396
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000109
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000216
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.113C>G (p.P38R) alteration is located in exon 1 (coding exon 1) of the BRI3 gene. This alteration results from a C to G substitution at nucleotide position 113, causing the proline (P) at amino acid position 38 to be replaced by an arginine (R). 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
0.28
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T;T
Eigen
Benign
0.18
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.47
T;T
M_CAP
Pathogenic
0.33
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.5
N;N
REVEL
Benign
0.084
Sift
Benign
0.34
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.99
D;P
Vest4
0.48
MutPred
0.51
Loss of glycosylation at P38 (P = 6e-04);Loss of glycosylation at P38 (P = 6e-04);
MVP
0.43
MPC
0.37
ClinPred
0.27
T
GERP RS
2.7
Varity_R
0.13
gMVP
0.44

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.

Other links and lift over

dbSNP: rs1423823612; hg19: chr7-97911220; API