Genetic Variant BRI3:p.Pro38Arg (chr7-98281908-C-G) – ACMG Classification: Uncertain_significance (1 pts)

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

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]

BRI3 links:

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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
BRI3	NM_015379.5 link	c.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
BRI3	ENST00000297290.4 link	c.113C>G	p.Pro38Arg	missense_variant	Exon 1 of 3	1	NM_015379.5	ENSP00000297290.3		O95415-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000208

AC:

AN:

4800

Hom.:

AF XY:

0.000350

AC XY:

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:

AN:

1144966

Hom.:

Cov.:

AF XY:

0.00000364

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.47

T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

PrimateAI

Uncertain

0.74

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

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.

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