chr12-124993929-C-A

Position:

• chr12-124993929-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000341446.9(BRI3BP):​c.139C>A​(p.Arg47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRI3BP ENST00000341446.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.409

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRI3BP	NM_080626.6	c.139C>A	p.Arg47Ser	missense_variant	1/3	ENST00000341446.9	NP_542193.3
BRI3BP	XM_011537940.3	c.139C>A	p.Arg47Ser	missense_variant	1/3		XP_011536242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRI3BP	ENST00000341446.9	c.139C>A	p.Arg47Ser	missense_variant	1/3	1	NM_080626.6	ENSP00000340761	P1
BRI3BP	ENST00000671775.2	c.139C>A	p.Arg47Ser	missense_variant	1/3			ENSP00000500775
BRI3BP	ENST00000672415.1	c.139C>A	p.Arg47Ser	missense_variant	1/3			ENSP00000500359	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1198438 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 590190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2022

The c.139C>A (p.R47S) alteration is located in exon 1 (coding exon 1) of the BRI3BP gene. This alteration results from a C to A substitution at nucleotide position 139, causing the arginine (R) at amino acid position 47 to be replaced by a serine (S). 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.29
MutPred		0.72		Loss of MoRF binding (P = 0.0154);
MVP		0.41
MPC		1.8
ClinPred		0.99	D
GERP RS		2.9
Varity_R		0.69
gMVP		0.70

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

Other links and lift over

dbSNP: rs1385268688; hg19: chr12-125478475;