chr12-125025197-C-A

Position:

• chr12-125025197-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080626.6(BRI3BP):​c.523C>A​(p.His175Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: BRI3BP NM_080626.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3049854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRI3BP	NM_080626.6	c.523C>A	p.His175Asn	missense_variant	3/3	ENST00000341446.9
BRI3BP	XM_011537940.3	c.316+12561C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRI3BP	ENST00000341446.9	c.523C>A	p.His175Asn	missense_variant	3/3	1	NM_080626.6	P1
BRI3BP	ENST00000671775.2	c.523C>A	p.His175Asn	missense_variant	3/3
BRI3BP	ENST00000672415.1	c.523C>A	p.His175Asn	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 14, 2023

The c.523C>A (p.H175N) alteration is located in exon 3 (coding exon 3) of the BRI3BP gene. This alteration results from a C to A substitution at nucleotide position 523, causing the histidine (H) at amino acid position 175 to be replaced by an asparagine (N). 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	0.32
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.036	D
Sift4G	Uncertain	0.058	T
Polyphen		0.76	P
Vest4		0.27
MutPred		0.37		Gain of ubiquitination at K176 (P = 0.0605);
MVP		0.40
MPC		1.0
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.37
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-125509743;