Variant 12-125012556-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080626.6(BRI3BP):c.236G>A(p.Arg79Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000551 in 1,612,370 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 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

BRI3BP
NM_080626.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Variant links:

Genes affected

BRI3BP (HGNC:14251): (BRI3 binding protein) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

BRI3BP links:

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=0.3536833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRI3BP	NM_080626.6 linkuse as main transcript	c.236G>A	p.Arg79Lys	missense_variant	2/3	ENST00000341446.9
BRI3BP	XM_011537940.3 linkuse as main transcript	c.236G>A	p.Arg79Lys	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BRI3BP	ENST00000341446.9 linkuse as main transcript	c.236G>A	p.Arg79Lys	missense_variant	2/3	1	NM_080626.6	P1
BRI3BP	ENST00000671775.2 linkuse as main transcript	c.236G>A	p.Arg79Lys	missense_variant	2/3
BRI3BP	ENST00000672415.1 linkuse as main transcript	c.236G>A	p.Arg79Lys	missense_variant	2/3			P1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000270

AC:

AN:

251472

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135908

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:

0.000139

Gnomad NFE exome

AF:

0.000571

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000579

AC:

846

AN:

1460162

Hom.:

Cov.:

AF XY:

0.000563

AC XY:

409

AN XY:

726492

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.000722

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000276

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000509

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

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

Mar 28, 2023

The c.236G>A (p.R79K) alteration is located in exon 2 (coding exon 2) of the BRI3BP gene. This alteration results from a G to A substitution at nucleotide position 236, causing the arginine (R) at amino acid position 79 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.026

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.40

MVP

0.48

MPC

1.7

ClinPred

0.23

GERP RS

4.1

Varity_R

0.76

gMVP

0.85

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