Genetic Variant NM_018688.6:c.346A>C (chr8-22624356-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018688.6(BIN3):c.346A>C(p.Ser116Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BIN3
NM_018688.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018688.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIN3	NM_018688.6	MANE Select	c.346A>C	p.Ser116Arg	missense	Exon 7 of 9	NP_061158.1	Q9NQY0-1
BIN3	NM_001363046.2		c.202A>C	p.Ser68Arg	missense	Exon 6 of 8	NP_001349975.1	H7BYV6
BIN3	NR_156436.2		n.416A>C		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIN3	ENST00000276416.11	TSL:1 MANE Select	c.346A>C	p.Ser116Arg	missense	Exon 7 of 9	ENSP00000276416.6	Q9NQY0-1
BIN3	ENST00000853250.1		c.358A>C	p.Ser120Arg	missense	Exon 7 of 9	ENSP00000523309.1
BIN3	ENST00000939253.1		c.283A>C	p.Ser95Arg	missense	Exon 7 of 9	ENSP00000609312.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000808

AC:

AN:

247454

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000587

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.0000450

AC:

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110940

Other (OTH)

AF:

0.00

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

0.93

Vest4

0.67

MutPred

0.58

Gain of MoRF binding (P = 0.0081)

MVP

0.66

ClinPred

0.95

GERP RS

5.4

Varity_R

0.76

gMVP

0.53

Mutation Taster

=60/40

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over