12-124993926-T-C

Position:

• chr12-124993926-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080626.6(BRI3BP):​c.136T>C​(p.Tyr46His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRI3BP NM_080626.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.122

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058132052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRI3BP	NM_080626.6	c.136T>C	p.Tyr46His	missense_variant	1/3	ENST00000341446.9
BRI3BP	XM_011537940.3	c.136T>C	p.Tyr46His	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRI3BP	ENST00000341446.9	c.136T>C	p.Tyr46His	missense_variant	1/3	1	NM_080626.6	P1
BRI3BP	ENST00000671775.2	c.136T>C	p.Tyr46His	missense_variant	1/3
BRI3BP	ENST00000672415.1	c.136T>C	p.Tyr46His	missense_variant	1/3			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1189420 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 585018

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

Sep 26, 2023

The c.136T>C (p.Y46H) alteration is located in exon 1 (coding exon 1) of the BRI3BP gene. This alteration results from a T to C substitution at nucleotide position 136, causing the tyrosine (Y) at amino acid position 46 to be replaced by a histidine (H). 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	0.30
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.038
Sift	Benign	0.42	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.33		Gain of disorder (P = 0.0274);
MVP		0.28
MPC		0.87
ClinPred		0.10	T
GERP RS		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.058
gMVP		0.59

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: chr12-125478472;