Variant 8-22624250-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018688.6(BIN3):c.452C>T(p.Thr151Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

BIN3
NM_018688.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.86

Variant links:

Genes affected

BIN3 (HGNC:1054): (bridging integrator 3) The product of this gene is a member of the BAR domain protein family. The encoded protein is comprised solely of a BAR domain which is predicted to form coiled-coil structures and proposed to mediate dimerization, sense and induce membrane curvature, and bind small GTPases. BAR domain proteins have been implicated in endocytosis, intracellular transport, and a diverse set of other processes. [provided by RefSeq, Jul 2008]

BIN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BIN3	NM_018688.6 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	7/9	ENST00000276416.11
BIN3	NM_001363046.2 linkuse as main transcript	c.308C>T	p.Thr103Met	missense_variant	6/8
BIN3	XM_047421995.1 linkuse as main transcript	c.290C>T	p.Thr97Met	missense_variant	4/6
BIN3	NR_156436.2 linkuse as main transcript	n.522C>T		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN3	ENST00000276416.11 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	7/9	1	NM_018688.6	P1	Q9NQY0-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000482

AC:

AN:

248840

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000639

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000496

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Feb 15, 2023

The c.452C>T (p.T151M) alteration is located in exon 7 (coding exon 7) of the BIN3 gene. This alteration results from a C to T substitution at nucleotide position 452, causing the threonine (T) at amino acid position 151 to be replaced by a methionine (M). 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

Uncertain

0.50

BayesDel_addAF

Benign

0.0015

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.59

D;.;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.79

MVP

0.76

ClinPred

0.62

GERP RS

5.4

Varity_R

0.37

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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