8-22623989-C-A

Variant names:

• chr8-22623989-C-A
• rs866436164
• NM_018688.6:c.541G>T

Variant summary

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

The NM_018688.6(BIN3):​c.541G>T​(p.Glu181*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BIN3 NM_018688.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN3	NM_018688.6	MANE Select	c.541G>T	p.Glu181*	stop_gained	Exon 8 of 9	NP_061158.1	Q9NQY0-1
	BIN3	NM_001363046.2		c.397G>T	p.Glu133*	stop_gained	Exon 7 of 8	NP_001349975.1	H7BYV6
	BIN3	NR_156436.2		n.611G>T		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN3	ENST00000276416.11	TSL:1 MANE Select	c.541G>T	p.Glu181*	stop_gained	Exon 8 of 9	ENSP00000276416.6	Q9NQY0-1
	BIN3	ENST00000853250.1		c.553G>T	p.Glu185*	stop_gained	Exon 8 of 9	ENSP00000523309.1
	BIN3	ENST00000939253.1		c.478G>T	p.Glu160*	stop_gained	Exon 8 of 9	ENSP00000609312.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	45
DANN	Uncertain	1.0
Eigen	Pathogenic	0.87
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		7.8
Vest4		0.33
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=82/118	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs866436164; hg19: chr8-22481502;